CDKN2A

General Information

Full gene name:cyclin-dependent kinase inhibitor 2A Entrez Gene ID:1029 Location:9p21 Synonyms:MTS-1, P16INK4A, ARF, P19ARF, CDKN2, MTS1, INK4, TP16, P16-INK4A, MLM, P14, CMM2, P16, P19, P14ARF, CDK4I, INK4A, P16INK4 Type:protein-coding

User SNPs

SNPs given by the user that are near or inside this gene:

SNP	Distance (bp)	Direction
rs10811661	139604	upstream

NCBI Summary

This gene generates several transcript variants which differ in their first exons. At least three alternatively spliced variants encoding distinct proteins have been reported, two of which encode structurally related isoforms known to function as inhibitors of CDK4 kinase. The remaining transcript includes an alternate first exon located 20 Kb upstream of the remainder of the gene; this transcript contains an alternate open reading frame (ARF) that specifies a protein which is structurally unrelated to the products of the other variants. This ARF product functions as a stabilizer of the tumor suppressor protein p53 as it can interact with, and sequester, MDM1, a protein responsible for the degradation of p53. In spite of the structural and functional differences, the CDK inhibitor isoforms and the ARF product encoded by this gene, through the regulatory roles of CDK4 and p53 in cell cycle G1 progression, share a common functionality in cell cycle G1 control. This gene is frequently mutated or deleted in a wide variety of tumors, and is known to be an important tumor suppressor gene. [provided by RefSeq, Jul 2008]

OMIM

OMIM ID:`OMIM ID 600160 `_

Allelic Variants (Selected Examples)

.0001 MELANOMA, CUTANEOUS MALIGNANT, SUSCEPTIBILITY TO, 2

Among the melanoma (155601) cell lines that carried at least 1 copy of CDKN2A (the other copy frequently being deleted), Kamb et al. (1994) identified a variety of nonsense, missense, or frameshift mutations. One of these was a G-to-A transition that converted gly259 to ser.

.0002 MELANOMA, CUTANEOUS MALIGNANT, SUSCEPTIBILITY TO, 2

Among 14 melanoma (155601) cell lines in which at least 1 copy of CDKN2A was present (the other copy frequently being deleted) and in which nonsense, missense, or frameshift mutations were identified, Kamb et al. (1994) found the same mutation in 2: a C-to-T transition converting codon 232 from arg to stop.

.0003 MELANOMA, CUTANEOUS MALIGNANT, SUSCEPTIBILITY TO, 2

Gruis et al. (1995) analyzed CDKN2A coding sequences in 15 Dutch FAMMM syndrome pedigrees, and identified a 19-bp germline deletion in 13 of them. All 13 families originated from an endogamous population. The deletion caused a reading-frame shift, predicted to result in a severely truncated p16 protein. Homozygosity for the deletion was found in 2 family members, one of whom showed no obvious signs of melanoma. The finding demonstrated that homozygotes for this CDKN2A mutation are viable, and suggested the presence of a genetic mechanism that can compensate for the functional loss of p16. The results strengthened the notion that p16 is the molecular nature of the 9p21-linked form of familial melanoma (CMM2; 155601). Of the 2 homozygous individuals, one was fully examined at the age of 54 and showed as the only possible sign of FAMMM 3 very mildly atypical nevi. Until her death from adenocarcinoma (site not stated) at the age of 55, this subject remained free of melanomas. The second homozygote, a nephew of the first, had a very large number of atypical moles at the age of 11; at the age of 15, an invasive melanoma was found.

(In addition to the 19-bp deletion of p16, which goes by the name of Leiden, there is at least one familial hypercholesterolemia Leiden (143890.0041), factor V Leiden (612309.0001), apoE3 Leiden (107741.0006), and a hemoglobin Leiden (141900.0156).)

Van der Velden et al. (1999) hypothesized that a tentative second tumor-related gene in 9p21 may also act as a modifier of melanoma risk conveyed by known CDKN2A mutations. To identify genetic modifiers for a known, ‘primary’ susceptibility gene, one would ideally need to study a large number of carriers of a single mutation in that primary gene. Dutch FAMMM families provided them with a unique opportunity for such studies, since the 19-bp founder deletion in exon 2 of the CDKN2A gene, p16-Leiden, segregated in most Dutch FAMMM families. The 36% cumulative incidence for melanoma in p16-Leiden carriers illustrated a high melanoma risk associated with this mutation but also suggested that environmental and/or genetic factors act as risk modifiers. Van der Velden et al. (1999) performed haplotype analysis for 9p21 using microsatellite markers in 6 p16-Leiden families originating from a founder population. In 2 families, p16-Leiden carriers shared an unexpectedly large founder haplotype (approximately 20 cM) around CDKN2A, mostly in the proximal direction. Melanoma-positive p16-Leiden carriers from these families showed this extensive proximal haplotype, compared with melanoma-negative p16-Leiden carriers from the same families. Additional p16-Leiden families less heavily affected with melanoma showed shorter haplotype sharing, excluding the region proximal of CDKN2A. The presence of a gene involved in melanoma susceptibility proximal to CDKN2A was corroborated by somatic deletions of 9p in tumors, which frequently did not include CDKN2A but a more proximal chromosomal region instead. The results provided a candidate region for further gene mapping in p16-negative 9p21-linked melanoma families and guided the search for risk modifiers in melanoma development.

Vasen et al. (2000) performed mutation analysis on 27 families with FAMMM syndrome and identified the CDKN2A-Leiden mutation (600160.0005) in 19 families. They identified 86 patients with melanoma, and the second most frequent cancer was pancreatic carcinoma, which was observed in 15 patients from 7 families. The mean age at diagnosis of pancreatic carcinoma was 58 years, with a range from 38 to 77 years. Putative mutation carriers had an estimated cumulative risk of 17% for developing pancreatic carcinoma by age 75 years. In the 8 CDKN2A-Leiden-negative families, no cases of pancreatic carcinoma had occurred. The authors concluded that individuals with the CDKN2A-Leiden mutation show an enormous risk of developing pancreatic cancer (see 606719).

Schneider-Stock et al. (2003) found the p16-Leiden mutation in heterozygous state in the blood and all 3 tumors of a man who was diagnosed at age 54 years with simultaneous development of 3 carcinomas of the pharynx and oral cavity. The patient neither smoked more than 5 cigarettes daily nor abused alcohol. Both his parents and his only sister died of cancer very early (the mother of gynecologic cancer, the father of liver carcinoma, and the sister of leukemia).

.0004 MELANOMA, CUTANEOUS MALIGNANT, SUSCEPTIBILITY TO, 2

In a family with melanoma (155601), Liu et al. (1995) found an in-frame deletion of 2 amino acids, asp96 and leu97, in 3 affected and 2 unaffected members. The mutation was a 6-bp deletion of nucleotides 363-368 of their CDKN2A sequence.

.0005 MELANOMA, CUTANEOUS MALIGNANT, SUSCEPTIBILITY TO, 2

In 3 families with melanoma (155601), Hussussian et al. (1994) identified a gly93-to-trp mutation in the CDKN2A gene. (The GLY93TRP mutation is now designated GLY101TRP.)

Whelan et al. (1995) described a kindred with an increased risk of pancreatic cancers, melanomas, and possibly additional types of tumors (see 606719) cosegregating with the gly93-to-trp CDKN2 mutation. Of interest was the occurrence of squamous-cell carcinomas in this family, a rare form, and squamous cell carcinoma of the tongue in the proband. More than half of primary esophageal squamous cell carcinomas have CDKN2 mutations (Mori et al., 1994). The mutation was identified by SSCP analysis and was located in exon 2 where direct sequencing demonstrated a G-to-T nucleotide change at position 295.

Ciotti et al. (1996) indicated that in a small geographic area of Italy (possibly because of founder effect), they had detected the gly93-to-trp mutation in 7 apparently unrelated families and in none of 50 control persons. Nineteen cases of melanoma and 3 of dysplastic nevi were diagnosed at ages ranging from 21 to 70 years in the kindreds with the G93W mutation. In addition, 15 cancers at other sites were found in these kindreds, including 3 pancreatic cancers but no gastric cancers. The pancreatic tumors developed in members of 3 different families at the ages of 48, 51, and 60 years.

Ciotti et al. (2000) stated that gly101-to-trp is the most common CDKN2A missense mutation, having been reported in numerous families from around the world, with a particularly high occurrence in France and Italy. They examined the date of origin of the mutation and its migratory spread in 10 families from Italy, 4 families from the U.S., and 6 families from France. In all families studied, the mutation appeared to have been derived from a single ancestral haplotype. Using maximum likelihood methods, they estimated that the mutation arose 97 generations ago, providing some explanation for the wide geographic spread of this common mutation, particularly in southwestern Europe. All of the Italian families, with one exception, came from a small area on the eastern coast of Liguria.

Auroy et al. (2001) found the G101W mutation in 7 patients with multiple primary melanomas with no known melanoma cases within their families. They stated that the mutation had already been described in more than 20 melanoma-prone families. They genotyped 8 microsatellite markers flanking the CDKN2A gene and found, after allowing for recombination over time, that haplotype sharing provided evidence for an original G101W mutation common to 6 of the 7 sporadic multiple primary melanoma cases.

In Italy, Mantelli et al. (2002) screened for CDKN2A mutations in families with 2 melanoma patients, 1 of whom was younger than 50 years at onset and the other complying with 1 of the following: being a first-degree relative; having an additional relative with pancreatic cancer; or having multiple primary melanomas. Mutations were found in 21 of the 62 families (34%) with a high prevalence of the G101W mutation (18 of 21).

.0006 MELANOMA, CUTANEOUS MALIGNANT, SUSCEPTIBILITY TO , 2

In 10 melanoma (155601) kindreds from southern Sweden, Borg et al. (1996) identified a novel germline mutation in 2 families, constituting an in-frame 3-bp duplication at nucleotide 332 in exon 2. The mutation resulted in an insertion of arg at codon 105, which interrupts the last of the 4 ankyrin repeats of the p16 protein, motifs which have been demonstrated as important in binding and inhibiting the activity of cyclin D-dependent kinases 4 and 6 in cell cycle G1 phase regulation. Other malignancies observed in gene carriers or obligate carriers included cervical, breast, and pancreatic carcinomas, and a non-Hodgkin lymphoma. Analysis of microsatellite markers adjacent to the p16 gene at chromosomal region 9p21 in the 2 families with the mutation showed that they shared a common haplotype, in keeping with a common ancestor.

By haplotype analysis, Hashemi et al. (2001) concluded that the mutation arose 98 generations, or approximately 2,000 years, ago. Thus, the mutation, which they designated 113insR, could be expected to have a more widespread geographic distribution in regions of Europe and North America with ancestral connections to Sweden. Alternatively, CDKN2A may lie in a recombination hotspot region, as suggested by the finding of many meiotic recombinations in a narrow region of approximately 1 cM on 9p21.

.0007 MELANOMA, CUTANEOUS MALIGNANT, SUSCEPTIBILITY TO, 2

Harland et al. (1997) identified a met53-to-ile (M53I) mutation in the CDKN2A gene in affected members of a family with melanoma (155601). They showed that the protein expressed from this previously described mutation did not bind to CDK4/CDK6 (see 123829), confirming its role as a causal mutation in melanoma. Monzon et al. (1998) found the same mutation in a patient with multiple melanomas who was thought to have no family history of melanoma when first investigated.

Pollock et al. (1998) pointed out that the M53I mutation had been described in 5 melanoma families from Australia and North America. Haplotype analysis suggested that there may have been only 1 original M53I mutation.

MacKie et al. (1998) identified this mutation in 4 U.K. melanoma families and also in 1 patient with multiple primary melanomas and a negative family history.

.0008 MELANOMA, CUTANEOUS MALIGNANT, SUSCEPTIBILITY TO, 2

In a patient with multiple primary melanomas (155601), Monzon et al. (1998) identified an arg24-to-pro mutation in the CDKN2A gene. They pointed out that this mutation had previously been reported in melanoma-prone families and was found to cosegregate with cases of melanoma. MacKie et al. (1998) identified this mutation in a U.K. melanoma family.

.0009 MELANOMA, CUTANEOUS MALIGNANT, SUSCEPTIBILITY TO, 2

Pollock et al. (1998) identified 2 new melanoma (155601) kindreds that carried a duplication of a 24-bp repeat present in the 5-prime region of the CDKN2A gene. This brought to a total of 5 the number of melanoma families described with this mutation; the 5 families were from 3 continents: Europe, North America, and Australasia. Previous families were reported by Goldstein et al. (1995), Walker et al. (1995), and Flores et al. (1997). This suggested to Pollock et al. (1998) that there had been at least 3 independent 24-bp duplication events. The duplication was hypothesized to have arisen due to an unequal crossing-over between the two 24-bp repeats naturally present in the wildtype sequence, possibly through polymerase slippage during replication. Further evidence that this repeat region is unstable and therefore prone to both meiotic and mitotic slippage was provided by the identification of a somatic 24-bp deletion of 1 of these normally occurring repeats in a prostate tumor (Komiya et al., 1995).

.0010 MELANOMA, CUTANEOUS MALIGNANT, SUSCEPTIBILITY TO, 2

Though germline CDKN2A coding mutations cosegregated with melanoma (155601) in 25 to 60% of families predisposed to the disease, there remain a number of mutation-negative families that demonstrate linkage of inherited melanoma to 9p21 markers (Hayward, 1996). Liu et al. (1999) showed that a subset of these kindreds possesses a G-to-T transversion at nucleotide -34 of CDKN2A, designated -34G-T. The mutation gives rise to a novel AUG translation initiation codon that decreases translation from the wildtype AUG. The -34G-T mutation was not seen in controls, segregated with melanoma in families, and, on the basis of haplotyping studies, appeared to have arisen from a common founder in the United Kingdom. Liu et al. (1999) suggested that screening for mutations in the promoter region of the CDKN2A gene should be useful in English (MacGeoch et al., 1994), Australian (Holland et al., 1995), and other northern European populations (Borg et al., 1996) in which a low incidence of germline coding mutations of CDKN2A has been found in familial melanoma cases.

.0012 MELANOMA AND NEURAL SYSTEM TUMOR SYNDROME

Randerson-Moor et al. (2001) described a family characterized by multiple melanoma and neural cell tumors (155755) segregating with a germline deletion of the p14(ARF)-specific exon 1-beta of CDKN2A. The deletion was approximately 14 kb and did not affect the coding or minimal promoter sequences of either CDKN2A or CDKN2B.

.0013 MELANOMA, CUTANEOUS MALIGNANT, SUSCEPTIBILITY TO, 2

One of the most common melanoma (155601)-related CDKN2A mutations reported in North America is val126 to asp (V126D). Goldstein et al. (2001) examined 9 markers surrounding the CDKN2A gene in 3 American and 4 Canadian families carrying this mutation. All 7 families had a haplotype consistent with a common ancestor/founder. The mutation appeared to have originated 34 to 52 generations ago; 1 lod unit supported an interval of 13 to 98 generations.

.0014 MELANOMA, CUTANEOUS MALIGNANT, SUSCEPTIBILITY TO, 2

Harland et al. (2001) reported that affected individuals in 6 of 90 English melanoma (155601) pedigrees screened carried a transition (IVS2-105 A-G) deep in intron 2 of the CDKN2A gene. The mutation creates a false GT splice donor site 105 bases 5-prime of exon 3 and results in aberrant splicing of the mRNA. The authors proposed that this mutation and others similar to it may account for a significant proportion of 9p21-linked melanoma pedigrees with no detectable mutations in the coding region of CDKN2A.

.0015 MELANOMA, CUTANEOUS MALIGNANT, SUSCEPTIBILITY TO, 2

Hewitt et al. (2002) reported a family harboring a splice mutation in exon 1-beta of the CDKN2A gene that resulted in ARF haploinsufficiency. The mutation was observed in a mother and daughter with melanoma and a sib of the mother with breast cancer. The mutation was a 334G-C transversion in exon 1-beta, which predicts a gly122-to-arg substitution. Its position at the 3-prime end of exon 1-beta raised the possibility of interference with splicing. Analysis of the melanoma from 1 individual revealed a 62-bp deletion in exon 3 of the wildtype allele and loss of the mutant allele; these somatic changes would affect both CDKN2A and ARF. The authors suggested that concomitant inactivation of both ARF and CDKN2A may be necessary for melanoma development and that mutations in ARF and CDKN2A possibly confer different levels of susceptibility to melanoma, with the former associated with lesser predisposition.

.0016 MELANOMA, CUTANEOUS MALIGNANT, SUSCEPTIBILITY TO, 2

A val59-to-gly mutation in the CDKN2A gene was found in 4 families segregating cutaneous malignant melanoma (155601): an Israeli family of Moroccan Jewish ancestry (Yakobson et al., 2001), 2 French families (1 of Tunisian Jewish ancestry and another without known Jewish roots) (Soufir et al., 1998), and a Spanish family (Ruiz et al., 1999). Yakobson et al. (2003) found that all but 1 of those affected in these families were heterozygous for the mutation; 1 affected member of the Israeli family was homozygous. Haplotype analysis indicated a single ancestral founder. The mutation, which occurs in a hydrophobic region with the second ankyrin repeat, impairs p16-INK4a function, as shown by studies of protein-protein interactions and cell proliferation assays.

.0017 MELANOMA, CUTANEOUS MALIGNANT, SUSCEPTIBILITY TO, 2

In 4 affected members from 3 families and 1 isolated patient with cutaneous malignant melanoma (155601), Kannengiesser et al. (2007) identified a heterozygous tandem germline 339G-C transversion and 340C-T transition in the CDKN2A gene, resulting in a leu113-to-leu (L113L) and a pro114-to-ser (P114S) substitution, respectively. All families were from southeastern France, and haplotype analysis indicated a founder effect. The sporadic patient had a high sun exposure history and Parkinson disease (168600) and received treatment with levodopa. He subsequently developed 22 primary melanomas, suggesting that levodopa may have contributed to the lesions. Further testing of this individual showed 2 pathogenic variants in the MC1R gene (see, e.g., R151C; 155555.0004), which likely contributed to the severe phenotype.

.0018 MELANOMA, CUTANEOUS MALIGNANT, SUSCEPTIBILITY TO, 2

In affected members of 3 families with cutaneous malignant melanoma (155601), Kannengiesser et al. (2007) identified a 167G-T transversion in the CDKN2A gene, resulting in a ser56-to-ile (S56I) substitution. Two patients were homozygous for the mutation, suggesting remote consanguinity. All families were from southeastern France, and haplotype analysis indicated a founder effect.

.0019 MELANOMA, CUTANEOUS MALIGNANT, SUSCEPTIBILITY TO, 2

Goldstein et al. (2008) identified a gly89-to-asp (G89D) variant in the CDKN2A gene that was associated with significantly increased risk for cutaneous malignant melanoma (155601) in an Icelandic population. The mutation results in a synonymous G143G change in the p14(ARF) protein. The frequency of the G89D variant was 0.7 in melanoma patients compared to 0.08 in controls. The association was strengthened when restricted to invasive melanoma, present in 2% of patients (p = 0.0015). Relatives of affected G89D carriers were at significantly increased risk of melanoma, head and neck cancers, and pancreatic carcinoma compared to relatives of other melanoma patients. Haplotype analysis indicated a founder effect. The common ancestor was determined to be a female who lived in Hunavatnssysla county in northern Iceland from about 1605-1665.

.0020 MELANOMA, CUTANEOUS MALIGNANT, SUSCEPTIBILITY TO, 2

In affected members of 2 unrelated Italian families with malignant melanoma (155601), Binni et al. (2010) identified a heterozygous A-to-G transition in exon 1B of the CDKN2A gene, affecting splicing of the p14(ARF) isoform. The families were ascertained from a large cohort of 155 Italian probands.

.0021 MELANOMA, CUTANEOUS MALIGNANT, SUSCEPTIBILITY TO, 2

In affected members of an Italian family with malignant melanoma (155601), Binni et al. (2010) identified a heterozygous 161G-A transition in exon 1B of the CDKN2A gene, resulting in an arg54-to-his (R54H) substitution in a highly conserved residue of the p14(ARF) isoform. The family was ascertained from a large cohort of 155 Italian probands.

NCBI Phenotypes

• Genome-wide association study identifies five new breast cancer susceptibility loci.
• New gene functions in megakaryopoiesis and platelet formation.
• Genome-wide association study of coronary artery disease in the Japanese.
• Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease.
• Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis.
• Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants.
• Genome-wide association study identifies a sequence variant within the DAB2IP gene conferring susceptibility to abdominal aortic aneurysm.
• Li-Fraumeni syndrome 1
• Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes.
• Genome-wide association study identifies three new melanoma susceptibility loci.
• OMIM
• Genome-wide association study identifies five susceptibility loci for glioma.
• Chromosome 7p11.2 (EGFR) variation influences glioma risk.
• A common variant on chromosome 9p21 affects the risk of myocardial infarction.
• Genome-wide association study of type 2 diabetes in a sample from Mexico City and a meta-analysis of a Mexican-American sample from Starr County, Texas.
• Confirmation of multiple risk Loci and genetic impacts by a genome-wide association study of type 2 diabetes in the Japanese population.
• GTR
• Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels.
• Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes.
• Gene Reviews
• Melanoma-pancreatic cancer syndrome
• A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants.
• Melanoma astrocytoma syndrome
• Genome-wide association study identifies three loci associated with melanoma risk.
• Susceptibility loci for intracranial aneurysm in European and Japanese populations.
• Genome-wide association study of intracranial aneurysm identifies three new risk loci.
• Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls.
• Melanoma, cutaneous malignant 2
• NHGRI GWA Catalog

Gene Ontology

• apoptotic DNA fragmentation
• mitotic cell cycle
• rRNA processing
• cell cycle arrest
• induction of apoptosis
• cytosol
• cytoplasm
• nuclear body
• positive regulation of macrophage apoptotic process
• positive regulation of DNA damage response, signal transduction by p53 class mediator
• negative regulation of protein kinase activity
• MDM2 binding
• negative regulation of cell-matrix adhesion
• protein destabilization
• cell cycle checkpoint
• NF-kappaB binding
• negative regulation of cyclin-dependent protein kinase activity
• protein binding
• DNA binding
• ubiquitin-protein ligase inhibitor activity
• negative regulation of cell proliferation
• positive regulation of transcription, DNA-dependent
• somatic stem cell division
• positive regulation of cellular senescence
• cyclin-dependent protein kinase inhibitor activity
• apoptotic mitochondrial changes
• p53 binding
• negative regulation of phosphorylation
• transcription, DNA-dependent
• positive regulation of smooth muscle cell apoptotic process
• protein complex
• senescence-associated heterochromatin focus
• negative regulation of immature T cell proliferation in thymus
• protein K63-linked ubiquitination
• protein polyubiquitination
• regulation of protein export from nucleus
• nucleus
• negative regulation of cell growth
• protein stabilization
• nucleoplasm
• positive regulation of protein sumoylation
• regulation of protein stability
• regulation of G2/M transition of mitotic cell cycle
• cellular senescence
• G1 phase of mitotic cell cycle
• transcription factor binding
• nucleolus
• senescence-associated heterochromatin focus assembly
• protein kinase binding
• G1/S transition of mitotic cell cycle
• replicative senescence
• Ras protein signal transduction
• negative regulation of NF-kappaB transcription factor activity
• positive regulation of transcription from RNA polymerase II promoter
• negative regulation of B cell proliferation
• activation of cysteine-type endopeptidase activity involved in apoptotic process
• negative regulation of ubiquitin-protein ligase activity
• positive regulation of cell cycle arrest
• negative regulation of transcription, DNA-dependent

KEGG Pathways

• HTLV-I infection
• Melanoma
• Glioma
• Bladder cancer
• Non-small cell lung cancer
• Pathways in cancer
• Pancreatic cancer
• Chronic myeloid leukemia
• p53 signaling pathway
• Cell cycle

GeneRIFs

• determined the p16 mutation spectrum for a cohort of 304 patients with Barrett’s esophagus; results suggest the environment of the esophagus in BE patients can both generate and select for clones with p16 mutations [PMID 19043591]
• The majority of tumours showed strong p16, p21, p27, pRb and cyclin D1 staining and little or no p53 expression. Tumours harbouring dysplasia were significantly more likely to be p53-positive and exhibit up-regulated p21 and p27. [PMID 19863319]
• A delay in p16INK4a induction and an extended lifespan of human keratinocytes when grown in co-culture with post-mitotic fibroblast feeder cells were identified. [PMID 16117791]
• Alterations in p14ARF gene by deletion and/or methylation were observed in 30% of the oral carcinoma cases. p14ARF methylation is associated with a lower recurrence rate. Promoter methylation of p16INK4A was associated with increased disease recurrence. [PMID 18268126]
• The p16INK4a/cyclin D1/pRB pathway was altered in gastrointestinal tract endocrine tumors [PMID 18794045]
• Tumor suppressor gene p16 and Rb expression in gastric cardia precancerous lesions from subjects at a high incidence area in northern China. [PMID 12046062]
• found homozygous deletion of p16/CDKN2A in 6 out of 7 cases of anaplastic astrocytomas and 20 out of 33 cases of glioblastoma multiforme, in total 26 out of 40 cases of malignant gliomas [PMID 19086579]
• p16 is induced as an "emergency brake" in cells experiencing sustained replicative stress within regenerative epithelial crypts in ulcerative colitis [PMID 16820088]
• Data show that Core inhibited p16 expression by inducing promoter hypermethylation via up-regulation of DNMT1 and DNMT3b. [PMID 21757290]
• the expression of DAP kinase, p19ARF, p53, and p21WAF1 was significantly down-regulated in the chronically HIV-1SF2-infected HUT78 T cells [PMID 15018706]
• alterations of the cell-cycle checkpoint controlling proteins p27(KIP1), p16(INK4a), and RB1 may exert a profound effect in malignant transformation in blastic plasmacytoid dendritic cell neoplasm [PMID 19924135]
• The t(8;21) fusion protein, AML1 ETO, specifically represses the transcription of the p14(ARF) tumor suppressor in acute myeloid leukemia. [PMID 12091906]
• geographical variation in the penetrance of mutations for melanoma [PMID 12072543]
• Findings confirmed that p16 overexpression is associated to high-grade precancerous lesions and cervical carcinomas, and demonstrated that immunohistochemical evaluation of p16 may be a useful biomarker in identifying HR-HPV-infected low-grade lesions. [PMID 16415792]
• Aberrant promoter methylation and reduced expression of p16 gene is associated with esophageal squamous cell carcinoma. [PMID 19513816]
• ERK activation with some other pathway(s), activated through the HGF receptor, are required to up-regulate p16 and p21 expression, that of p21 contributes to suppression of Cdk2 activity leading to inhibition of proliferation of HGF-treated HepG2 cells. [PMID 18004740]
• Hypermethylation of p16 is associated with recurrence of bladder cancer. [PMID 20800513]
• ARF is a serine phosphorylation-dependent coregulator of topoisomerase I in vivo, and it regulates cellular sensitivity to camptothecin by interacting with topoisomerase I. [PMID 18004878]
• p16 Immunoreactivity in unusual types of cervical adenocarcinoma does not reflect human papillomavirus infection [PMID 20727021]
• A better understanding of ARF’s nucleolar interactions could further elucidate the regulation of the p53 pathway and suggest new therapeutic approaches to restore p53 function. [PMID 16855788]
• investigation of the involvement of the CDKN2A, CDKN2B and p53 genes in actinic keratosis (AK) and in the progression of AK to squamous cell carcinoma [PMID 18331779]
• simultaneous detection of p53, Rb, p16, and EGFR in a suspension microarray facilitates rapid diagnosis of lung cancer [PMID 20082263]
• Genetic and epigenetic analyses of the human 9p21 locus indicate that modifications of ARF occur independently of p16 inactivation in human melanoma and suggest that ARF is more frequently inactivated than p16. [PMID 18505964]
• Arf is haploinsufficient for the induction of acute myeloid leukemia in the presence of the inv(16) [PMID 16199529]
• Affinity Capture-Western; Reconstituted Complex [PMID 18583933]
• Activation of the Cyclin D1 promoter by ErbB3 is regulated by p14ARF. [PMID 22261253]
• MDM2 amplification in 3 cases, all at diagnosis and relapse and p14(ARF) inactivation in 12 of 41 (29%) cases: 3 had p14(ARF) methylation. [PMID 20145180]
• the factors modifying significantly the melanoma risk associated with CDKN2A mutations (stepwise procedure) were: MC1R and dysplastic nevi (increasing the risk) and GSTT1 (decreasing the risk). [PMID 19484507]
• Loss of p16 and increased incidence of autosomal aneuploidy and chromatid breaks, along with other chromosomal alterations, can contribute to the progression of lung cancer. [PMID 20444664]
• p14(ARF) inhibits Tat transactivation of HIV-1 LTR by promoting Tat degradation via an ubiquitin-independent pathway. [PMID 18418067]
• ISOC2 is a novel functional protein, which is able to bind and co-localize with a tumor suppressor gene p16(INK4a). [PMID 17658461]
• data show that the CDKN2A p.G23S mutation is an important cause of hereditary melanoma in Tuscany [PMID 17992122]
• Three samples with mutations identified at the local centres were not detected by DHPLC. The low rate of CDKN2A mutation detection is not due to failure to detect mutations and implies the existence of other high penetrance melanoma susceptibility genes. [PMID 18394881]
• nm23 does not appear to be a more useful biomarker than p16 in identifying cervical intraepithelial neoplasia 2 or high-risk human papillomavirus infection. [PMID 20955383]
• Results suggest that GC- II is the key site for Sp1 binding and increase of Sp1 binding activity rather than protein levels contributes to the induction of p16(INK4a) expression during cell aging. [PMID 17225865]
• Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator) [PMID 21037509]
• Percentage of cases with p16 staining decreased significantly with increasing degree of dysplasia of aerodigestive tract [PMID 16948516]
• P16 hypermethylation in mucosa of colorectal cancer patients was identified as an independent prognostic parameter for cancer-specific survival. [PMID 18418463]
• EBV LMP1 blocks p16INK4 pathway by promoting nuclear export of E2F-4 and E2F-5. [PMID 12860972]
• Study show that polymorphisms in CDKN2A were associated with type 2 diabetes risk in the studied population. [PMID 18694974]
• regulation of p14(ARF) gene by E2F is distinct from that of classical E2F targets; results indicate that the distinct regulation constitutes the basis of p14(ARF) function as a tumor suppressor [PMID 16211008]
• Acute myeloid leukemia (AML) derived blasts show a down-regulation of p16(INK4a) mRNA with increasing age. Suppression of defense mechanisms which protect older cells against DNA damage might facilitate oncogenesis in older individuals. [PMID 20157576]
• p16INK4A and p14ARF are complementary and should be evaluated jointly in order to improve the accuracy of cytological diagnosis of cervical cancer. [PMID 22072122]
• found increased susceptibility of melanocytes to oxidative stress in the context of p16 depletion, which may explain why the compromise of p16 predisposes to melanoma over other cancers [PMID 20838381]
• PAX5 is a common target in leukemogenesis of B-ALL along with CDKN2A. Owing to its frequent deletion in B-ALL. No correlation between expression of PAX5 and deletion of PAX5 suggests allele-specific regulation. [PMID 21549623]
• Down-regulation of p16INK4A mRNA is associated with acute myeloid leukemia at older age. [PMID 19667402]
• Frequent p16INK4a promoter hypermethylation is associated with human papillomavirus-infected female lung cancer [PMID 15455389]
• hypermethylation of the p16INK4A promotor region is a frequent and an early event during thyroid carcinogenesis and is associated with tumor progression and dedifferentiation [PMID 12924440]
• These findings confirm that loss of p16 function could be involved in pancreatic cancer and may explain at least in part the aggressive behaviour of this tumor type. [PMID 15985168]
• expression of the nuclear p16INK4A form and strong expression of the cytoplasmic p16INK4A form both represent two independent parameters each associated with tumour progression in gastrointestinal stromal tumours [PMID 20459531]
• Promoter hypermethylation of the p16 gene is associated with poor prognosis in recurrenct early-stage hepatocellular carcinoma. [PMID 18723830]
• P16 protein is closely related with the occurrence of nasal inverted papilloma. [PMID 19522184]
• Report expression of p16(INK4A) gene in human pituitary tumours. [PMID 18058237]
• p16(INK4a) is a valuable biomarker for detection of HPV-related dysplastic squamous cells. [PMID 17980098]
• Use of p16INKra immunocytochemistry can improve the prognostic statement in routine procedure for patients with cervical intraepithelial neoplasia. [PMID 15915391]
• All HPV-positive and -negative cervical cancer cell lines expressed p16(INK4A) protein, and that indicates the existence of dysplasia or malignancy in the uterine cervix, regardless of HPV infection. [PMID 15998377]
• Low levels of p14ARF mRNA in leukemic cells from patients with normal karyotype AML is associated with poor prognosis. [PMID 19626541]
• Expression of Galectin-3, CD138, p16INK4a, and TTF-1 in mucinous bronchioloalveolar adenocarcinoma after Hodgkin lymphoma. [PMID 18997617]
• Promoter hypermethylation of p16 occurs at an early stage of cervical neoplastic progression. [PMID 21436693]
• Data show that methylation of CCND-2, p16, RAR-beta and RASSF-1a was significantly more prevalent in tumor than in normal tissue specimens. [PMID 19618401]
• Affinity Capture-Western [PMID 17588519]
• Ink4a/arf plays a critical role in UV-induced melanomagenesis. [PMID 12438273]
• analysis of coexisting NRAS and BRAF mutations in primary familial melanomas with specific CDKN2A germline alterations [PMID 19759551]
• the ability to promote Lys(63)-mediated polyubiquitination of COMMD1 is a novel property of ARF independent of p53 [PMID 18305112]
• The pattern of the p14(ARF) expression is not associated with the alterations of other TP53 pathway members in advanced-stage human Endometrial carcinomas. [PMID 20683407]
• study concludes that p16 gene is involved in the pathogenesis of skin basal cell carcinoma in view of increased p16 mRNA and expressed protein within tumor cells [PMID 18760195]
• an important role for p16 gene in the cell cycle regulation of multiple myeloma tumor cells [PMID 12199782]
• We immunohistochemically analyzed the expression of p21, p27, p14, p16, p53 and proliferation marker Ki67, in 67 low and high grade astrocytic tumors [PMID 18181833]
• Observation that silencing of p16 expression augments DNA damage-induced apoptosis in cervical cancer cells offers alternative strategies for anti-cancer therapies for human cervical cancer. [PMID 17369842]
• p16(ink4a) plays a role in the radiation resistance of chondrosarcoma cell lines and suggests that restoring p16 expression will improve the radiation sensitivity of human chondrosarcomas. [PMID 16765318]
• The overexpression of p16 in uterine serous carcinoma is unrelated to HPV. [PMID 17581420]
• alterations in both p53 and p16ink4a can contribute to recessive dystrophic epidermolysis bullosa-associated squamous cell carcinoma [PMID 15373786]
• Systemic processes may affect this region of 9p21 at times during melanoma progression. [PMID 12296515]
• diffuse, strong positivity with p16 protein suggests an endocervical rather than an endometrial origin of an adenocarcinoma [PMID 12819388]
• Data find that following reprogramming, epigenetic silenced p16 expression is restored and is stably maintained even when cells are induced to differentiate. [PMID 20572015]
• The effect of pH on the expression of p16 and NOX5-S on Barrett’s esophagus cells and their progression to esophageal adenocarcinoma are reported. [PMID 20576920]
• Deficiency of CDKN2A and PTEN expression, although shared across many other different types of tumors, likely represents a key aspect of chordoma pathogenesis [PMID 21602918]
• study indicated that p16 expression was reduced in adenoid cystic carcinoma cases of higher histological grade of malignancy and that hypermethylation of its promoter gene may be involved in its process in some cases [PMID 12624503]
• hypermethylation of the p16 and Wif-1 genes has potential as biomarkers that may be used to predict the prognosis of stage IA NSCLC [PMID 19787276]
• CDKN2A plays an important role in laryngeal squamous cell carcinoma development and progression [PMID 15083191]
• rs10811661 of CDKN2A/B confers risk for type 2 diabetes. [PMID 21625859]
• Protein expression neither of p16(INK4a) nor of p53 correlated with high-risk human papillomavirus status [PMID 18021213]
• Inactivation of p16 gene in histologically normal bronchi could aid the identification of individuals at risk of developing squamous cell carcinoma of the lung. [PMID 18315600]
• distinct methylation pattern in bladder cancer with frequent methylation of RARbeta, DAPK, E-cadherin, and p16. [PMID 11839665]
• p14ARF induces p53-dependent cell cycle arrest but not apoptosis [PMID 15701968]
• Highest frequencies of DNA methylation in p16 gene were found in head and neck squamous cell tumours with aneuploidy. [PMID 21115918]
• AID-mediated genotoxic effects appear to occur frequently at the CDKN2b-CDKN2a locus and contribute to malignant transformation of the gastric mucosa [PMID 20637757]
• Data found homozygous deletions in exon 3 of the p16INK4a gene in two schwannomas. [PMID 18551412]
• CDKN2A deletion is associated with acute lymphoblastic leukaemia. [PMID 18989737]
• Mitochondrial p32/C1QBP is a critical mediator of p14ARF-induced apoptosis. [PMID 18538737]
• significant difference was detected between esophageal cancer and non-tumorous tissue in p16 expression; a significant correlation was observed among p53, COX-2 and p16 expression [PMID 17650224]
• Oncogene-induced senescence does not require the p16(INK4a) or p14ARF melanoma tumor suppressors. [PMID 19212341]
• analysis of P53, p16 and Ki67 immunoexpression in oral squamous carcinomas [PMID 22395505]
• Ink4a-Arf deficiency allows for GBM formation from astrocytes and that it enhances tumor incidence in neural progenitor cells. [PMID 12359767]
• This evaluation of the diagnostic performance of p16 cytology confirms the potential of this stain for the efficient triage of ASC-US and LSIL cytologic results. [PMID 20551261]
• p14(ARF) hypermethylation was detected in 16 (53.3%) of hepatocellular carcinoma [PMID 18683194]
• Review of molecular mechanisms underlying the functional loss of cyclindependent kinase inhibitors p16 and p27 in hepatocellular carcinoma. [PMID 18350604]
• ARF is able to counteract the suppression of Miz-1 on p53 by direct binding to Miz-1 [PMID 19901969]
• Affinity Capture-Western; Two-hybrid [PMID 19901969]
• Results show that overexpression of CDK4, cyclin D1, and Rb proteins, and loss of expression of proteins p16, p27, and p19 were statistically significant in NPC tissues compared with non-cancerous NPE (P<0.05) by real-time RT-PCR and tissue microarray. [PMID 19430707]
• Our study revealed significantly enhanced expression of p16(INK4a)/p14(ARF) mRNA in cervical scrapes referred to as HSIL compared with normal women. [PMID 22080060]
• Expression of p16 increased with uterine cervical lesion progression [PMID 18300235]
• Loss of p16-related cell cycle regulation may be associated with the development of Epstein-Barr virus-related gastric carcinoma. [PMID 15459500]
• Germline mutations in CDKN2A among unselected pancreatic cancer patients are uncommon, although notably penetrant, especially among smokers. [PMID 21150883]
• splice site mutations do predispose to disease in a subset of melanoma-prone kindreds [PMID 14508519]
• downregulation by Id-1 expression [PMID 12016143]
• Data show that proteinnbinding and subcellular localization can accurately and rapidly determine the functional significance of melanoma-associated p16(INK4a) mutations. [PMID 20340136]
• p14ARF signals through hAda3 to stimulate p53 acetylation and the induction of cell senescence [PMID 17452980]
• Promoter methylation of p16 is a promising biomarker for malignant transformation of OED. [PMID 18708411]
• Affinity Capture-Western; Reconstituted Complex; Two-hybrid [PMID 11278317]
• SPINO interacts with p14ARF. [PMID 11278317]
• expression is related to apoptosis in thymus [PMID 11642719]
• p16 may be involved in the pathogenesis of high-grade ovarian serous carcinomas [PMID 19188815]
• correlation between p16 gene deletion and mammary gland carcinoma [PMID 17642181]
• Observational study of genotype prevalence and gene-disease association. (HuGE Navigator) [PMID 15705881]
• Expression of p16 was significantly correlated with unfavorable prognosis in gastrointestinal stromal tumors. [PMID 17917670]
• GRIM-19/CDKN2A synergistically suppressed cell cycle progression via inhibiting E2F1-driven gene expression. [PMID 20522552]
• Linkage of flat mole count to the CDKN2A gene region (9p21)was replicated with in 424 families with 1024 twins and siblings, plus genotypes for 690 parents. [PMID 17063143]
• in head and neck squamous cell carcinoma low dietary intake of folate is associated with p16(INK4A) methylation, and this relationship is modified by the methylene tetrahydrofolate reductase genotype [PMID 16646054]
• Poorly differentiated colorectal adenocarcinomas strongly correlates with miscrosatellite instability and methylation of the p16 and hMLH1 promoter region. [PMID 18161865]
• Affinity Capture-Western; Reconstituted Complex [PMID 20208519]
• p16 Methylation was correlated with malignant transformation of oral epithelial dysplasia and is a potential biomarker for prediction of prognosis of mild or moderate oral epithelial dysplasia. [PMID 19671846]
• Authors describe the characterization of a novel strain of human diploid fibroblasts (designated Milan HDFs) from an individual who is homozygous for the R24P mutation in p16INK4a. [PMID 17909018]
• c-MET and INK4a/ARF, situated at the nexus of pathways regulating myogenic growth and differentiation, represent critical targets in rhabdomyosarcoma pathogenesis [PMID 12368906]
• Data demonstrate that Bmi1 promotes prostate tumorigenesis, and that Bmi1 expression is associated with a reduction in tumor suppressors p16(INK4A) and p14(ARF). [PMID 18817867]
• p16 inactivation by promoter methylation has different effects in non-small cell lung and colorectal cancer: clinical implications [PMID 14719111]
• p16 mutations were found in 50% of pancreatic adenocarcinoma cell lines and 75% of primary tumors. They were mostly missense/deletion/frameshift mutations in exon 2. [PMID 15367885]
• There are different immunohistochemical expression patterns of p16INK4A and p53 between intraductal papillary-mucinous neoplasm and pancratic intraepithelial neoplasm [PMID 17198188]
• Tumors with methylated CDKN2A are more sensitive to zebularine than those with deleted CDKN2A. The combination of zebularine/depsipeptide results in a synergistic effect on cell growth inhibition that is also linked with the presence of silenced CDKN2A. [PMID 20811718]
• overlapping E2F1/Sp1 site, being present in multiple copies in the p14ARF promoter, may serve as the targets for both E2F1 and Sp1, thereby playing a crucial role in response to some oncogenic signals and stimulators [PMID 19115249]
• Smoking was not associated with p16 or ppENK hypermethylation in pancreatic cancer patients [PMID 17198183]
• Methylation of the p16 gene was detected more frequently in nontumorous liver than in normal liver using the TaqMan PCR method. Methylation indices also were significantly higher in nontumorous than in normal liver. [PMID 19016326]
• activation of hTERT alone appears to be insufficient for immortalization of prostate epithelial cells because methylation of p16(INK4a) promoter has been found to be involved in the immortalization process [PMID 18383581]
• lesions showed positive immunostaining of p53, affecting to the lower two thirds of the epidermis in BD and bAK, and only the basal layer in non-bAK. All the BD and bAK cases were positive for p16 [PMID 19515076]
• The CDKIs p16 and p27 are associated with tumour progression in melanoma, but do not reliably predict recurrence or survival. [PMID 18027257]
• data demonstrated p16 promoter methylation in a highly tumour specific pattern in oral squamous cell carcinoma [PMID 16449996]
• High-risk human papillomavirus E6/E7 mRNA detection by a novel in situ hybridization assay strongly correlates with p16 expression and patient outcomes in oropharyngeal squamous cell carcinoma. [PMID 21836494]
• p16 and PTCH have roles in pathogenesis of melanoma and basal cell carcinoma [PMID 19287961]
• The p16INK4a gene methylation is significantly associated with hgiher Dukes; stage. [PMID 22218684]
• p16INK4A to be a key factor in the regulation of human mesenchymal stem cells growth and is associated with cellular senescence. [PMID 17569790]
• The A148T variant of the CDKN2A gene is not associated with melanoma risk in the French and Italian populations. [PMID 16614725]
• Finding questions the role of p16(INK4a) promoter methylation as a negative prognostic factor in DLBCL. [PMID 21035853]
• Promoter hypermethylation was observed in PRB 67%, ERalpha 64%, RASSF1A 63%, p16INK4A 51%, RARbeta2 22%, GSTP1 25% and BRCA1 27% of the breast cancers, respectively. [PMID 19940364]
• study of EGFR, HER2, TP53& KRAS mutations of p14arf expression of non-small cell lung cancers in relation to smoking [PMID 17575133]
• The expressions of CDK4 and Cyclin D1 increased along with progression of gallbladder mucosa hyperplasia and p16 decreased to the lowest level in gallbladder cancer. [PMID 21777578]
• Overexpression of p16 protein in the cytoplasm and decreased expression of p16 protein in the nucleus may play important roles in the evolution of pleomorphic adenoma to carcinoma in the salivary gland. [PMID 21732778]
• Because p16(INK4a)-positive cells were detected only in premalignant lesions and carcinomas but not in normal or benign tissues, p16(INK4a) may aid in the diagnosis of PIN and prostate cancer in difficult cases. [PMID 16799475]
• p16-marker testing does not add value to the conventional 3-marker (ER/Vim/CEA) panel in distinguishing between primary endocervical adenocarcinomas and endometrial adenocarcinomas [PMID 19696622]
• Low p16(Ink4a) expression, overexpression of p53, cytoplasmic p27(Kip1), and Cyclin A are predictive markers for shorter overall survival in ovarian carcinomas. [PMID 21464733]
• Decreased expression of p16 in dysplastic lesions, as found in this study, may reflect the biologic events involving loss of p16 gene function in the pathogenesis of oral cancer. [PMID 16799478]
• The cytoplasmic immunoreactivity of p16 appears to be an unfavorable prognostic indicator in high-grade astrocytoma patients. [PMID 16614947]
• genetic alterations of p16 gene are rare events in patients with CLL; Sequencing of these cases revealed the presence of the ALA148THR polymorphism. Methylation analysis of p16 gene promoter revealed hypermethylation of CpG islands in 6/34 cases (17.6%). [PMID 16412137]
• novel germline mutation in exon 1 of the CDKN2A gene, E27X, which we first detected in melanoma patients living in or originally from a small geographic area bordering Liguria in north-western Italy [PMID 16893909]
• the CDKN2a locus is a switch in PCa with methylation of p16(INK4a) being a marker for more aggressive tumours of Gleason score 7b, but no association with BMI overexpression was observed. [PMID 21912429]
• As2O3 treatment caused demethylation associated with an increase in mRNA levels of the CDKN2B and CDKN2A genes. [PMID 20596618]
• Methylation of p16INK4a may contribute to the malignant progression of gastric MALT lymphomas. [PMID 16357845]
• elevated level of histone methylation resulted in the downregulation of the p16(Ink4a) gene [PMID 17544373]
• chromobox homolog 7 represses p16Ink4a and p14Arf expression in normal and tumor-derived prostate cells, affecting their growth [PMID 15897876]
• Meta-analysis and HuGE review of gene-disease association. (HuGE Navigator) [PMID 19602701]
• HPV infection is present in more than half of penile cancers and it is responsible for RB p16 INK4A pathway disruption [PMID 21323963]
• p16 INK4A positivity identifies endometrial surface papillary syncitial change as a regressive feature associated with desquamation [PMID 21323964]
• loss of P16 protein by promoter methylation results in non small cell lung tumorigenesis [PMID 11920642]
• Controls the retinoblastoma protein pathway to trigger its antiproliferative function. [PMID 16501607]
• Deletions in the CDKN2A locus and hypermethylation in the CDKN2A promoter region play a role in ovarian granulosa cell tumorogenesis. [PMID 12203782]
• regulates cell cycle [PMID 12101670]
• Data report that p16INK4a interacts with the chromatin remodelling factor BRG1. [PMID 19149898]
• Affinity Capture-Western; Two-hybrid [PMID 19149898]
• combined data support the premise that ARF induces autophagy in a p53-independent manner in part by virtue of its interaction with Bcl-xl [PMID 19049976]
• low p16 expression due to methylation may contribute to tumor enlargement and expansion of colorectal cancer [PMID 15809712]
• aberrant hypermethylation of the key cell cycle regulatory genes occurs at a relatively high frequency in pituitary adenomas, especially in RB1 pathway genes with promoter hypermethylation of the p16(INK4a) gene being the most common deregulation [PMID 17216555]
• Loss of p16(Ink4a) expression occurs during malignant transformation and is caused mainly by aberrant methylation of the CDKN2A promoter. [PMID 21423154]
• Results suggest that methylation of the p15(INK4B) and p16(INK4A) genes is an epigenetic biomarker of pediatric disease evolution. [PMID 20658957]
• Results show that p14ARF regulates E2F-1 ubiquitination and degradation via a p53-dependent mechanism. [PMID 17630509]
• Study suggested that p16 overexpression might play a role in the development and progression of pituitary adenomas. [PMID 11775544]
• Mdm2 interacts with p14ARF. [PMID 10822382]
• p38 MAPK and JNK antagonistically control senescence and cytoplasmic p16INK4A expression in doxorubicin-treated endothelial progenitor cells [PMID 21187925]
• ARF can inhibit c-Myc by a unique and direct mechanism that is independent of p53 [PMID 15361884]
• p14ARF interacts with c-Myc. [PMID 15361884]
• E-cadherin and p16INK4a are commonly methylated in non-small cell lung cancer [PMID 15254707]
• conclude that HPV does not play an indispensable role in the development of urinary bladder inverted papillomas and that overexpression of p16(Ink4a) does not correlate with HPV infection in these tumors [PMID 20036459]
• Nondysplastic leukoplakias without dual p53p16INK4a and triple p53p16INK4aKi-67 aberration seem to be harmless. Nondysplastic leukoplakias with these aberrations are at risk of progression, with very promising positive predictive value. [PMID 21435003]
• Analysis of the pattern of expression of these biomolecules showed increased p16-positive phenotypes and decreased cyclin D1- and pRB-positive phenotype among the invasive tumors compared to low-grade CIN lesions [PMID 18306932]
• The methylation of p16 gene lead to the inactivation of p16 gene and was related with the carcinogenesis and progress of SCC of buccal mucosa. [PMID 16784614]
• P16(INK4A) was overexpressed in 71.7% of Hodgkin lymphoma, was in the nucleus and cytoplasm of HRS cells, and was inversely related to EBV-LMP1 [PMID 19099554]
• p16 overexpression is associated with oropharyngeal cancer. [PMID 20423915]
• No mutations of the CDKN2A tumour suppressor gene were detected among patients with melanoma and additional cancers. [PMID 12459645]
• Histopathological features of cutaneous malignant melanomas from families with mutations in the CDKN2A gene are described. [PMID 12459644]
• p16 promoter hypermethylation is associated with gastric cancer patients [PMID 12824886]
• Keratinocytes of chronic psoriatic plaques were characterized by enhanced p16, p14(ARF), and p12 expression accompanied by elevated Egr-1 levels [PMID 12507899]
• Study is the first to report a large CDKN2A germline deletion with a breakpoint located within an exon. [PMID 17001621]
• Homozygous deletion, a combination of LOH and promoter hypermethylation, and multiple LOH are major mechanisms of p16 inactivation in gallbladder cancer. [PMID 18081229]
• P16(INK4a) expression measured by RT-PCR did not correlate with the cytological diagnosis or HPV status in cervical screening. [PMID 19910796]
• Aberrant promoter methylation was investigated by methylation-specific real-time PCR for p16, p14, APC and hMLH1. [PMID 21538028]
• There was no statistically significant difference in the percentage of methylation of the DAPK genes (Fisher test, p = .190) and p16 gene (Fisher test, p = .316) between the vulvar lichen sclerosus group (study) and the control group. [PMID 22371043]
• The results of this study suggested that CDKN2A and CDKN2B do not act as a risk factors for Alzheimer’s disease. [PMID 21069533]
• Genotypes of rs10757278 linked to increased risk of atherosclerotic diseases are also associated with decreased expression in PBTL of the INK4/ARF locus [PMID 19343170]
• p16(INK4A) overexpression is a useful additional marker for the interpretation of problematic uterine cervical lesions [PMID 20400236]
• p16(INK4A) seems to be a sensitive biomarker of high grade cervical intraepithelial neoplasia and cancer. [PMID 19372590]
• Our study suggested that mutation/hypermethylation/allelic alterations (LOH/MA) of CDKN2A were associated with the development of dysplastic head and neck lesions. [PMID 14586645]
• CDKN2A polymorphism is a potential indicator of melanoma predisposition among first-degree relatives of patients with malignant melanoma. [PMID 12950144]
• We suggest that p16(INK4a) may regulate gene expression by modifying the functional equilibrium of transcription factors and consequently the expression balance of miRNAs [PMID 21170085]
• p16 ink4a and L1 immunohistochemistry can be helpful for estimating the biologic potentiality of low-grade squamous cervical lesions [PMID 18769337]
• Results demonstrated concordant loss of p16 proteiin and MTAP expression in pancreatic intraepithelial neoplasia. [PMID 15832197]
• these data suggest that p16(INK4a) play a role in the poor prognosis of BLBC. [PMID 20661408]
• Methylation of the p16 is associated with advanced esophageal squamous cell carcinoma [PMID 17094449]
• Age does not appear to be a major indicator of CDKN2A or CDK4 mutations in melanoma patients in Spain [PMID 16314743]
• CDKN2A germ-line mutations is associated with cutaneous malignant melanoma [PMID 16896043]
• Expression of wild-type p16(INK4a) and p53 genes in K562 cells results in reduced proliferation and apoptosis. Co-transfection with both genes significantly inhibited cell proliferation when compared to transfection with either p16(INK4a) or p53 gene. [PMID 11836163]
• Founder deletion (p16-Leiden) in Dutch melanoma families does not account for the atypical nevus phenotype that segregates in both p16-Leiden carriers and non-carriers and is a risk factor and a precursor lesion for melanoma. [PMID 18398432]
• a high level of expression of MIB-1 indicates a low grade of tumor, whereas high expression of p16INK4a indicates a highly differentiated cervical adenocarcinoma [PMID 18202755]
• Methylation in the p16 promoter region is biologically significant, being associated with phosphorylation of pRb and cell growth in human hepatocellular carcinoma cells [PMID 16254459]
• five types of traditional Chinese medicine can attenuate G1 growth arrest of HaCaT cells and dermal fibroblasts induced by UVB exposures, which was caused by down-regulating the expression of cell-cycle regulatory proteins p16, p21 and p53. [PMID 21729169]
• role in progession of mycosis fungoides [PMID 11850526]
• This analysis is most consistent with the model that p16(INK4a) expression monotonically increases with age, and higher expression is associated with increased subject attrition. [PMID 19805338]
• Helicobacter pylori upregulates the expression of p16(INK4) in gastric cancer SGC7901 cells via the p16(INK4) promoter [PMID 21830402]
• Methylation of INK4a is associated with the development of malignant pancreatic disease [PMID 12610506]
• p16 expression was seen in 40% of esophageal dysplasia, 27% of esophageal squamous cell carcinoma and 100% of normal mucosa. [PMID 17060721]
• The study included a total of 28 cases of urothelial carcinomas, which were analyzed histopathologically and immunohistochemically using anti-human p16, c-erbB2 and Ki67 antibodies. [PMID 21655657]
• Knockdown of SIRT1 abolished GR-induced p16 repression as well as Akt/p70S6K1 activation implying that SIRT1 may affect p16 repression through direct deacetylation effects and indirect regulation of Akt/p70S6K1 signaling. [PMID 21390332]
• The variation in CDKN2A mutations is consistent with the lower melanoma incidence rates in Europe and higher rates of sporadic melanoma in Australia. [PMID 16905682]
• In summary, p16 methylation is very frequent among non-small cell lung carcinoma patients, and correlates with heavy cigarette consumption only in disease-free smokers. [PMID 17923809]
• Regulation of DNMT1 and DNMT3A by HBx promoted hypermethylation of p16(INK4A) promoter region [PMID 20620135]
• Mel-18 overexpression showed reduced glycogen synthase kinase-3beta phosphorylation, beta-catenin nuclear localization, T-cell factor/lymphoid enhancer factor promoter activity, and cyclin D1 mRNA level [PMID 18519679]
• show that downregulation of p300 histone acetyltransferase activity induces senescence by a mechanism that is independent of the activation of p53, p21(CIP1) and p16(INK4A). [PMID 21915115]
• Epstein-Barr virus-encoded latent membrane protein 1inhibited p16(INK4A) expression, promoted phosphorylation of p105 Rb and upregulated E2F1 expression and overexpression of E2F1 alone was sufficient to upregulate telomerase activity. [PMID 17597480]
• Primary cutaneous diffuse large B-cell lymphoma, leg type is characterized by a high frequency of aberrations of the CDKN2A network components. [PMID 21410763]
• Immunohistochemical analysis of MA2/D2-40 combined with p16(INK4A) may have a significant implication in clinical practice for better identifying the grade of cervical intraepithelial neoplasia. [PMID 21729305]
• The present study was performed to estimate the frequency of methylated p16INK4A in the sera of patients with hepatitis C virus related liver diseases. [PMID 20802412]
• Inactivation of p16INK4a as a critical event for overcoming telomere-independent crisis, immortalizing MRC5 fibroblasts and overcoming ras-induced premature senescence. [PMID 15308640]
• Genistein induces the expression of tumor suppressor genes p21 (WAF1/CIP1/KIP1) and p16 (INK4a) with a concomitant decrease in cyclins in prostate cancer cells. [PMID 18413741]
• p16 and retinoblastoma protein determines response to CDK4/6 inhibition in ovarian cancer [PMID 21278246]
• Following transfection of the ribozyme construct in pancreatic cancer cells, mutant p16 mRNA molecules were repaired and p16 protein synthesis restored. [PMID 15336553]
• These findings implicate MBD2 in transcriptional repression of the methylated p14(ARF) tumor suppressor gene and suggest that repression by MBD2 selectively affects a subset of methylated promoters. [PMID 18931530]
• p16 is a useful marker for the discrimination between cervical and pulmonary squamous cell carcinomas. [PMID 19369633]
• senescence of primary NHP cells expressing progenitor cell markers CD44, alpha2beta1, p63, hTERT, and CK5/CK18, involves loss of telomerase expression, up-regulation of p16, and activation of p53. [PMID 18662989]
• Hypermethylation of p16, RUNX3, and HPP1 in Barreett exophagus may represent independent risk factors for the progression of Barrett esophagus to esophageal cancer. [PMID 15824739]
• CDKN2A mutation is associated with melanoma [PMID 15577313]
• Loss of heterozygosity (LOH) of the hDMP1 gene was detectable in approximately 35% of human lung carcinomas, which was found in mutually exclusive fashion with LOH of INK4a/ARF or that of P53. DMP1 is a pivotal tumor suppressor for human lung cancers. [PMID 17936562]
• A total of 33% (68/204) of the families harbored cyclin-dependent kinase inhibitor 2A mutations in Italian melanoma [PMID 19500876]
• Observational study of gene-disease association and genetic testing. (HuGE Navigator) [PMID 19500876]
• c.-21C > T CDKN2A variant is a melanoma-predisposing mutation. [PMID 20093296]
• A paucity of mutations in CDKN2A/ARF suggesting that in the Polish population this gene does not contribute significantly to early-onset breast cancer, pancreatic cancer and malignant melanoma. [PMID 18714178]
• Upon p14ARF overexpression, UBF was found hypophosphorylated, thus unable to efficiently recruit the transcription complex, these data define a new p53-independent pathway that could regulate cell cycle through the negative control of rRNA transcription. [PMID 16924243]
• Results indicate that p14ARF aberrant promoter methylation could be involved in bladder carcinogenesis and that plasma DNA is a potential prognostic marker in urinary bladder cancer. [PMID 11948103]
• High expression of p16 leads to loss of the pRb protein and this two factors are inversely correlated in urothelial carcinoma.(p16) [PMID 20890425]
• Reduced expression of p16 is associated with leiomyosarcoma. [PMID 20680693]
• hSNF5 binds the p16INK4a and p21CIP/WAF1 promoters, suggesting that it directly regulates transcription of these genes. [PMID 16288006]
• ONL001702281 [PMID 20526108]
• CDKN2A (p16INK4a) interacts with MAPK8 (JNK1) [PMID 16007099]
• CDKN2A (p16INK4a) interacts with MAPK10 (JNK3) [PMID 16007099]
• we provided evidence for a crucial role for direct inhibition of p53 by MDM2 and suppression of the p19(ARF)/p53 axis in neuroblastoma tumorigenesis [PMID 19649205]
• MDM2 interacts with p14ARF [PMID 9653180]
• p16 methylation was significantly associated with H. pylori infection in precancerous gastric lesions, suggesting that H. pylori infection could potently induce methylation of p16 CpG island [PMID 18821580]
• alteration of p16 could play an etiologic role, without any association to HPV infections, in rare endometrial carcinomas [PMID 17498885]
• Results show that in human fibroblasts, ARF is not induced demonstrably by RAS, pointing to significant differences between the proliferative barriers implemented by the CDKN2A locus in different cell types or species. [PMID 12065407]
• Data show that the high sensitivity of MS-qFRET enables one-step detection of methylation at PYCARD, CDKN2B, and CDKN2A genes in patient sputum samples that contain low concentrations of methylated DNA, which normally would require a nested PCR approach. [PMID 19443857]
• Recent findings in P16 regulation are reviewed in this study, as well as their significance in understanding the role of P16 in cancer from a biochemical perspective. [PMID 21619050]
• Reconstituted Complex; Two-hybrid [PMID 15065884]
• Reconstituted Complex [PMID 15065884]
• germline epimutation of the CDKN2A gene is not found in familial melanoma [PMID 18818678]
• The study shows a strong correlation between high-risk HPV infection and p16(INK4a) expression in patients with squamous cell cancer of oral cavity and oropharynx. [PMID 21225495]
• p16(INK4a) distribution did not correlate with smokeless tobacco keratosis (STK) grade and does not appear to be related to the detection of HPV DNA by PCR in either STK or in squamous cell carcinoma. [PMID 18606525]
• The Arf-dependent assembly of this complex leads to the repression of multiple genes involved in cell adhesion and signal transduction and induces apoptosis. [PMID 20308430]
• p16 in the development of PA and in the progression of pleomorphic adenoma (PA) and carcinoma ex pleomorphic adenoma (CXPA) of the parotid gland. [PMID 17927591]
• A significant relationship was found between the presence/absence of p16(INK4A) staining in oral squamous cell carcinoma (OSCC) and the presence/absence of p16(INK4A) staining in lesions preceding [PMID 20955378]
• many human cell types undergo senescence by activation of the p16(INK4a)/Rb pathway, and that introduction of Bmi-1 can inhibit p16(INK4a) expression and extend the life span of human epithelial cells [PMID 17233832]
• An association between p16INK4 and CIN2 and CIN3 lesions was found which may indicate that p16INK4 may be a strong marker for "neoplastic lesions" induced by HPV and not just an infection marker. [PMID 18719739]
• Data identified loss of p16 and upregulation of MDR-1 at protein level with chromosomal translocation in the established cell lines. [PMID 21325069]
• benign columnar epithelium in the setting of cervical microglandular hyperplasia can be expected to stain strongly for p16. [PMID 19188826]
• In this immunohistochemical study, 80% of all vulvar intra-epithelial neoplasia were positive of p16(INK4A). [PMID 18798277]
• CDKN2B (p15(INK4b)), CDKN2A (p16(INK4a), p14(ARF)), and MTAP are abundantly expressed in atherosclerotic lesions. [PMID 20637465]
• Cirrhotic livers reveal genetic changes in the MDM2-P14ARF system of cell cycle regulators. [PMID 11953887]
• In melanocytic lesions, p16INK4A and NF-kappaB p65 expression were inversely correlated with levels of the nuclear component of NF-kappaB p65. [PMID 15297971]
• X protein of hepatitis B virus (HBx) overcomes cellular senescence provoked by a universal premature senescence inducer, H(2)O(2), in human hepatoma cells by repressing p16(INK4a) expression via DNA methylation. [PMID 19656618]
• Alterations in genetic and epigenetic status of p14ARF is associated with osteosarcoma growth [PMID 11943335]
• p16(INK4A) as a highly specific marker of CIN and HR-HPV type, but expression of this protein does not seem to be of any prognostic value in cervical cancer or in predicting the clearance of HR-HPV after treatment [PMID 15381905]
• Activation of caspase-3 and cleavage of Rb are associated with p16-mediated apoptosis in human non-small cell lung cancer cells. [PMID 11960384]
• p16INK4a/pRb may function as an alternative pathway of oncogene-induced senescence; the reactivation of p16INK4a expression might be a novel strategy to restore the senescence program in some tumors. [PMID 21518927]
• laminin 5 and p16INK4A have roles in wound healing and senescence [PMID 16723698]
• Epigallocatechin-3-gallate can activate and up-regulate the expression of p16 in the malignant lymphoma cell line CA46. [PMID 18928598]
• ability to promote SUMO conjugation is a general property of the p14 Arf tumor suppressor [PMID 15355988]
• p14 interacts with WRN. [PMID 15355988]
• p14 interacts with MDM2. [PMID 15355988]
• Hypermethylation of P14ARF is associated with bladder cancer. [PMID 20683150]
• TP53, CDKN1A, CDKN2A, and CDKN2B have roles in tumorigenesis in skin melanomas, but none of them is a main mutation target for melanoma tumorigenesis [PMID 15819981]
• association of the two genes hMLH1 and CDKN2A/p16 may allow a differential diagnosis between benign and premalignant/malignant endometrial lesions. [PMID 19697618]
• p16 may be implicated in the development of high-grade serous neoplasia within the ovary and elsewhere within the female genital tract. [PMID 17493241]
• Affinity Capture-MS; Affinity Capture-Western [PMID 21139048]
• Oncolytic herpes virus with defective ICP6 specifically replicates in quiescent cells with homozygous genetic mutations in p16. [PMID 18345032]
• determination that p16 is not activated in hTERT immortalization of urothelial cells [PMID 16619045]
• Hypermethylation of the CDKN2A gene is associated with colorectal cancer [PMID 12792748]
• Inactivation of p16INK4A in intestinal and diffuse subtypes of gastric adenocarcinoma showed distinct carcinogenic pathways and the process of methylation of the CDKN2A promoter seems to depend on the H. pylori genotype depending on the tumor location [PMID 20402675]
• Mutation of p16 and Rb genes might be correlated with progression of gallbladder carcinoma [PMID 15655836]
• p14(ARF) down-regulates E2F-dependent transcription. In cells undergoing E2F-dependent apoptosis it arrests the cell cycle. p14(ARF) has multiple binding domains for E2F-1, one within the N-terminal region coinciding with the regulation of E2F activity. [PMID 12082609]
• p14ARF interacts with E2F-1. [PMID 12082609]
• inactivation of both p16(INK4a) and pRb is associated with immortalization of human cells including fibroblasts and epithelial cells and telomerase-positive cells and ALT-positive cells [PMID 12507935]
• human cytomegalovirus(HCMV)infection stimulates the expression of p16(INK4a); evidence provided that p16(INK4a) upregulation plays a positive role for HCMV replication [PMID 16504234]
• The expression of p16(INK4A) protein is significantly higher in endocervical adenocarcinoma than in endometrial adenocarcinoma [PMID 18346352]
• Data suggest that loss of heterozygosity at 9p21 appears to play an important role in gastrointestinal stromal tumor progression, as decreased p16 expression in GIST is highly predictive of poor outcome. [PMID 20872974]
• Loss of CDKN2A gene at 9p21 may contribute to the progression and malignant transformation of gastrointestinal stromal tumors. [PMID 20972908]
• Effect of mutation on nevus distribution. [PMID 16354203]
• findings suggest that hepatitis B virus X protein may play an important role in the early stage of HBV-associated hepatocarcinogenesis via induction of hypermethylation of p16(INK4A) promoter [PMID 17539963]
• dermoscopic features of early melanoma in CDKN2A mutation-positive Spanish individuals; mean +/- SD ABCD total dermoscopy score (TDS) was significantly higher in noncarriers of red hair MC1R polymorphisms than in carriers of 2 MC1R gene red hair variants [PMID 18795926]
• The M53I mutation in CDKN2A is a founder mutation that predominates in melanoma patients with Scottish ancestry [PMID 17171691]
• Need for a deeper exploration for the use of p16(INK4a) as a surrogate marker with the potential to impact the standard of care of HPV DNA-positive head and neck carcinomas. [PMID 20091864]
• p21(Waf1) can activate the transcription of p16(INK4); this effect is GC-box dependent; and the transcription factor Sp1 plays a key role in this event [PMID 15094066]
• In 50 of the 66 primitive colorectal tumor cases at least one significant alteration was identified in Ki-Ras and/or TP53 and/or p16(INK4A) genes. [PMID 16760301]
• This study shows thap p16in4a expression was significantlyh increased in both high-grade squamous intraepithelial lesions and cervical squamous carcinoma compared with low-grade squamous intraepithelial lesions [PMID 22299207]
• Positive expression of p16, Ki-67, and ProEx C and negative expression of p53 seem to be related to HPV-16 infection [PMID 19687314]
• Apak is differentially regulated in the ARF and ATM-dependent manner in response to oncogenic stress and DNA damage, respectively. [PMID 20713054]
• The p16, DAPK and RAR beta genes methylation are strongly associated with clinical data of non-small cell lung cancer, and methylation of p16 and DAPK genes are associated with tobacco smoking. [PMID 21287504]
• Observational study and genome-wide association study of gene-disease association. (HuGE Navigator) [PMID 20512145]
• found that expression of CBX7 in gastric carcinoma tissues with p16 methylation was significantly lower than that in their corresponding normal tissues, which showed a negative correlation with transcription of p16 in gastric mucosa [PMID 21060834]
• Alterations of SH3GL2 and CDKN2A loci have a synergistic role in the development of early-onset breast cancer. [PMID 18239974]
• p16INK4A gene plays an important role in the pathogenesis of hepatocellular carcinoma. [PMID 15012776]
• expression at different stages of bladder cancer [PMID 12073046]
• inactivation may not play an important role in the malignant transformation of ependymomas [PMID 11763427]
• Data show that the rs10811661 polymorphism near the CDKN2B/CDKN2A genes is associated with impaired insulin release and IGT, suggesting that this variant may contribute to type 2 diabetes by affecting beta cell function. [PMID 21234743]
• Human tumor suppressor ARF impedes S-phase progression independent of p53. [PMID 11861400]
• involvement of p14(ARF) in the development of pancreatic cancer [PMID 14679123]
• 27/30 (90%) of Atypical lipomatous tumor (ALT)/well-differentiated liposarcoma (WDLPS) showed positive staining of either p16, MDM2, or both, whereas no staining was observed in all the deep-seated lipomas [PMID 18779733]
• It might be possible that HPV infection and mutations in the exon 2 of CDK4 play a causal role in malignant transformation in a small number of squamous carcinomas of the head and neck region. [PMID 17340131]
• Changes in the p53, MDM2, and p14(ARF) protein levels were not correlated with 5-year survival rate of esophageal squamous cell carcinoma. [PMID 19488782]
• senescence-responsive regulation of gene expression [PMID 19409979]
• Aberrant expression of pRb and p16, alone and in combination, heralds poor prognosis in patients with CRC. [PMID 15492985]
• deletion predicts relapse in children with ALL treated according to the Nordic protocols NOPHO-86 and NOPHO-92 [PMID 12357355]
• Inactivation of CDKN2A and B genes constitute an important step in chordoma development. [PMID 18071362]
• p16INK4a modulates glycomic profile and galectin-1 expression to increase susceptibility to carbohydrate-dependent induction of anoikis in pancreatic carcinoma cells [PMID 17535296]
• p16(INK)overexpression was found to be a reliable marker for high-risk HPV and a helpful tool in the differential diagnosis of low-grade verruciform and high-grade solid penile tumors. [PMID 21263246]
• combined with screening of K-ras mutations and allelic losses of tumor suppressors p16 and DPC4 represents a very sensitive approach in screening for pancreatic malignancy. [PMID 17659731]
• Results suggest that p16 immunohistochemistry alone is the best test to use for risk stratification in oropharyngeal squamous cell carcinoma. [PMID 20588174]
• Nordihydroguaiaretic acid reverses p16INK4a CpG island hypermethylation, and restores its transcription and expression in human breast and colorectal cell lines. [PMID 18164318]
• Type 2 diabetes susceptibility of CDKN2A was confirmed in Japanese. [PMID 19033397]
• High expression of the p14ARF gene is associated with chronic lymphocytic leukemia. [PMID 22047081]
• Lack of p16/CDKN2A deletion significantly predicted the survival of malignant mesothelioma patients. [PMID 18958493]
• p14ARF mRNA expression was suppressed in 13 of 37 cases of ATLL, among which 9 cases showed inactivation of both p14ARF and p16INK4a, and 4 cases showed inactivation of p14ARF alone. inactivation of p14ARF and mutation of p53 are mutually exclusive. [PMID 18246599]
• The methylationn frequency in malignant pleural mesothelioma was 11.4%. Methylation did not correlate to outcome but to improved survival in unmethylated malignant pleural mesothelioma with extrapleural pneumonectomy. [PMID 17920725]
• nucleophosmin in the nucleolus, ARF utilizes an additional mechanism of tumor suppression, one that is readily antagonized by Mdm2 [PMID 15485902]
• Gene expression modulated by hnRNP A1 and hnRNP A2 RNA binding proteins [PMID 12209876]
• In human colon cancer cell lines,the expression of the p16(INK4A) gene is regulated by DNA methylation. [PMID 15059516]
• In 109 patients (90 squamous cell carcinomas, 19 adenocarcinomas), we found that hypermethylation of the APC1A gene promoter occurred in 8.3% of patients, and of p16INK4a in 1.8%. [PMID 21674126]
• p16INK4a overexpression seems to be a useful tool for discriminating differentiated from warty, basaloid, and warty-basaloid penile intraepithelial neoplasia. [PMID 20139761]
• The p16 gene promoter was hypermethylated in pterygia, and this hypermethylation was strongly linked to expression of the positive expression of DNMT3b protein and to the suppression of p16 protein. [PMID 17149367]
• review of p15INK4b, p14ARF and p16INK4a function as cell cycle inhibitors where they are involved in the inhibition of G1 phase progression, and promoter methylation in hematologic malignancies and solid tumors [PMID 15370242]
• The expression of p16 was significantly higher in tumorous tissues than in non-tumorous ones. A significant relationship was observed between p53 and COX-2, or p16 and COX-2. But no obvious correlation was seen between p53 and p16 expressions. [PMID 16481301]
• A c-Kit low-polysomy profile seems to parallel CDKN2A homozygous deletions in pediatric melanoma whereas the single activating mutation observed segregates with familial patients [PMID 19158841]
• Promoter histone H3 lysine 9 di-methylation along with DNA methylation and aberrant expression of p16 is associated with gastric cancer. [PMID 19787243]
• Immunofluorescence technology to quantify cervical cell expression of two biomarkers p16(INK4A) and Mcm5 was developed and evaluated by both microscopy and flow cytometry. [PMID 18181189]
• Simultaneous measurement of p16 and L-ras mutations provides an additional tool in differential diagnosis of chronic pancreatitis and pancreatic adenocarcinoma. [PMID 15608367]
• P16INK4A is overexpressed in HR-HPV-infected cervical cancer, but its tumor suppressor action might be inhibited. [PMID 17672936]
• p16 alterations and particularly p16 gene deletions in endometrial carcinoma are associated with increased incidence of metastases. [PMID 18790522]
• Deletions of p16INK4a gene are uncommon and loss of p16 protein expression is a common event in melanoma [PMID 14719109]
• p16 interacts with cdk6. [PMID 8805225]
• p16 interacts with cdk4. [PMID 8805225]
• Reconstituted Complex [PMID 15107860]
• p16 methylation may be one of the earliest events in the pathogenesis of esophageal squamous cell carcinoma and is also observed in reflux esophagitis. [PMID 22169643]
• identified inactivating deletions within CDKN2A as a candidate poor prognostic marker of CRTC1-MAML2 positive mucoepidermoid tumors [PMID 19827123]
• these results reveal the novel role of IKKbeta in P16 phosphorylation and broaden our understanding of the regulation of P16. [PMID 20152798]
• Hepatitis B virus X protein overcomes trans retinoic acid-induced cellular senescence by downregulating levels of p16 and p21 via DNA methylation. [PMID 21325480]
• Our data suggest that Bmi-1 extends the replicative life span of human fibroblasts by suppressing the p16-dependent senescence pathway. [PMID 12482990]
• methylation of the INK4A/ARF locus is not a disease-specific molecular change in mononuclear cell fraction; the p14ARF and p16INK4A genes are differentially methylated [PMID 16320052]
• Tumor suppressor p16INK4a determines sensitivity of human cells to transformation [PMID 14585357]
• senescence induced by the forced expression of p16 in early passage IMR90 fibroblasts or osteosarcoma U2OS cells was accompanied by expression of the two most acidic p16 variants [PMID 15668906]
• Compared to other minimally invasive tumor markers, such as NMP22, the expression of p16INK4a in cytology specimens of urine appears to be a sensitive marker for urothelial carcinoma, especially for the detection of poorly differentiated carcinomas. [PMID 21847682]
• Down-regulation of p16INK4A is associated with severity of cervical lesions. [PMID 20069634]
• Homozygous deletion and hypermethylation of p16 gene may play an important role in the initiation and development of manifestations seen in endemic arseniasis including carcinogenesis. [PMID 17479413]
• data suggest that p16INK4a expression in cytology of ascites is a candidate marker in prediction of the primary response to chemotherapy and prognosis [PMID 19330839]
• We did not find p16, p14, and p57 to be useful as prognostic markers in stage III ovarian cancer [PMID 17885492]
• This study suggests that P16/CDKN2A gene inactivation in asbestos-exposed non-small-cell lung cancer cases mainly occurs via deletion. [PMID 19375815]
• Affinity Capture-MS; Affinity Capture-Western; Protein-peptide; Reconstituted Complex; Two-hybrid [PMID 17353931]
• Affinity Capture-MS [PMID 17353931]
• Downregulation of p16(INK4a) and loss of wild-type p53 expression occurs after escape from cell immortalization [PMID 14743210]
• Report an estradiol-inducible adenovirus-mediated gene transfer system for nuclear delivery of a p16INK4A-estrogen receptor carboxy terminal fusion protein. [PMID 20198335]
• results suggest that p16 is up-regulated or accumulated in small cell carcinomas (SmCCs) of the uterine cervix, probably caused by infection with human papillomavirus; p14 inactivation is of high prevalence in SmCCs [PMID 16633070]
• p16 and p14ARF have roles in radio- and chemosensitivity of malignant gliomas [PMID 16786135]
• CDKN2A, GATA3, CREBBP, ITGA2, NBL1 and TGM4 were down-regulated in the prostate carcinoma glands compared to the corresponding normal glands [PMID 21743959]
• founder mutation (ins113Arg) in one family and a large duplication encompassing the CDKN2A gene locus in another family; moreover, a debated polymorphism (Ala148Thr) was found in nine families [PMID 17255954]
• INK4a-ARF mutations are infrequent outside stringent familial criteria, and germline INK4a-ARF deletions are rarely involved in genetic predisposition to melanoma [PMID 14735200]
• No significant associations were observed between p16 homozygous deletions and gender, age, smoking history, stage, and prognosis. [PMID 18559592]
• the ARF tumor suppressor interacts with VHL30, a longer VHL isoform, but not with VHL19, a shorter VHL isoform [PMID 21942715]
• Affinity Capture-MS; Affinity Capture-Western [PMID 21942715]
• Data show that in patients with squamous cell carcinoma of the tongue, p14(ARF) expression predicts for improved survival independent of established prognostic markers. [PMID 15930346]
• MEOX1 and MEOX2 activate p16(INK4a) in a DNA binding dependent manner, whereas they induce p21(CIP1/WAF1) in a DNA binding independent manner. [PMID 22206000]
• in ovarian carcinomas, findings show that patients with high positivity for p53, p16(INK4a) and Cyclin D1 had a poor prognosis and reduced overall survival [PMID 21956468]
• p16 immunostaining was noted in the majority of conventional and desmoplastic trichilemmomas [PMID 19461237]
• PIWIL4 might play an oncogenic role in cervical cancer [PMID 22483988]
• No significant relation was observed between aberrant DNA methylation of P16, MGMT and hMLH1 gene, as well as MTHFR C677T genetic polymorphisms and the prognosis of esophageal squamous cell carcinoma. [PMID 21375764]
• p16gamma, like p16(INK4A), induced cell-cycle arrest at G(0)/G(1), and inhibited cell growth in colony formation assay. [PMID 17486064]
• p16gamma: a novel transcriptional variant of p16INK4A [PMID 17486064]
• results demonstrate a different expression profile between p16(INK4a) and p14(ARF), p15(INK4b) and p53 in BCC and a low percentage of LOH and of a polymorphic sequence variant (Ala148Thr) for the CDKN2A locus. [PMID 19298278]
• E2a-Pbx1 and Bmi-1 are likely to play a role in the pathogenesis of human lymphoid leukemias through downregulation of the INK4A-ARF gene [PMID 14536079]
• CDKN2A/p16+ test reporting enhances compliance with early detection measures for melanoma families. [PMID 18559569]
• Homozygous CDKN2A/p14(ARF)/CDKN2B deletion plays an important role in pleomorphic xanthoastrocytoma. [PMID 16909113]
• CDKN2A (chromosome 9p) has been analyzed for loss of heterozygosity in T-cell lymphoblastic lymphoma (T-LBL) and T-cell lymphoblastic leukemia (T-ALL). LOH at 9p was detected in 47% of T-LBL and 51% of T-ALL and is associated with male gender in both. [PMID 19586936]
• analyzed the methylation status of the promoter region of the CDKN2A gene in gastric adenocarcinomas; CDKN2A promoter methylation was not significantly associated with microsatellite instability [PMID 12514789]
• HPV may be involved in the carcinogenesis of some colorectal neoplasms but p16INK4A does not seem to be a surrogate marker for an active HPV infection. [PMID 20346145]
• The nucleolar p19(ARF) is incapable of inducing autophagy from within the nucleolus. [PMID 18719357]
• Results reveal a molecular mechanism of ARF in regulating ribosome biogenesis and cell proliferation via inhibiting B23. [PMID 14636574]
• ARF activates p53, at least partly by induction of ribosomal stress, which results in L11 suppression of MDM2 [PMID 22467867]
• This is the first study indicating that MSP analysis of p16(INK4a) and p14(ARF) genes is a useful biomarker for the pathological stage, clinical outcome, and prognosis of patients with bladder cancer. [PMID 16316628]
• Overexpression of p16 and CDK4 in the cytoplasm, as well as loss expression of p16 in the nucleus might be important in the evolution of colorectal carcinoma from adenoma and, of adenoma from normal epithelia. [PMID 17072968]
• Aberrant methylation in p16 gene promoter in the sediment cells of pleural effusion specimens show the difference between benign and malignant pleural effusion. [PMID 20855275]
• p16INK4A, DAPK1, PTEN and MT1G genes were not frequently methylated in the stage I non-small cell lung cancer in China. [PMID 19506903]
• cooperates with CARF in activating p53 [PMID 12154087]
• The abnormal expression of the gene p16 might play an important role in the formation of fibrous dysplasia. [PMID 19575869]
• expression of p14(ARF) does not significantly alter ribosome biogenesis but inhibits polysome formation and protein translation [PMID 17035234]
• Affinity Capture-Western; Reconstituted Complex [PMID 12556559]
• Promoter region of p16INK4a showed a decrease in 5-methylcytosine following in vitro exposure to ischemia. [PMID 20543577]
• The 2 physiological nuclear export signal motifs mediated NPM1 homo/heterodimerization, influencing subcellular distribution of NPM1wt, mutated NPM1 and p14(ARF) in a ‘dose-dependent tug of war’ fashion. This event is critical for leukaemogenesis. [PMID 19005479]
• P16INK4 is required for human fibroblast senescence and for limiting ras-induced epithelial cell proliferation as evidenced from siRNA-directed "knock down." [PMID 14720514]
• Glutathione S-transferase P1 and NADPH quinone oxidoreductase polymorphisms are associated with aberrant promoter methylation of P16(INK4a) and O(6)-methylguanine-DNA methyltransferase in sputum. [PMID 11956078]
• Lowered p16 expression represented an unfavourable prognostic index in ovarian cancer. [PMID 18283637]
• Meta-analysis of gene-disease association. (HuGE Navigator) [PMID 18431743]
• Elevated expression of cell-cycle regulators p16(INK4A), p21(CIP1), and cytoplasmic/nuclear beta-catenin correlated with increased colorectal cancers risk, as did elevated expression of survivin and human telomerase reverse transcriptase. [PMID 17641414]
• cases with inactivation of all p14(ARF), p15(INK4b), and p16(INK4a) genes showed the worst prognosis in a combined prognostic assessment [PMID 21262917]
• The activation of ATM/ATR/CHK signaling pathways contributes to this G2 checkpoint and highlight the interrelated roles of p14ARF and the Tip60 protein in the initiation of this DNA damage-signaling cascade. [PMID 16705183]
• Affinity Capture-Western; Reconstituted Complex [PMID 16705183]
• CDKN2A is the main familial pancreatic cancer predisposition gene in Italian families. [PMID 22368299]
• NIAM is a nuclear interactor of ARF and Mdm2 [PMID 18582208]
• Human p14(ARF)-mediated cell cycle arrest strictly depends on intact p53 signaling pathways. [PMID 12082636]
• Adenovirus-mediated overexpression of p14(ARF) induces p53 and Bax-independent apoptosis. [PMID 12082630]
• MITF regulates p16INK4A expression in melanocytes. [PMID 15623583]
• Signaling events required for G1 cell cycle arrest and apoptosis induction by p14 ARF dissociate upstream of p53. [PMID 15750619]
• p16 methylation may be a predictor of BRCA1 mutation status [PMID 20056647]
• Implication of genetic variant near CDKN2A in type 2 diabetes in a Chinese population is reported. [PMID 20509872]
• A two-stage, p16(INK4A)- and p53-dependent keratinocyte senescence mechanism that limits replicative potential independent of telomere status. [PMID 12077343]
• the correlation between anal intraepithelial neoplasia and p16 is strong enough to be quite useful in distinguishing true AIN from benign mimics [PMID 18301250]
• HLE B-3 cells were successfully transduced with adenovirus-mediated antisense c-myc construct. Ad-AS-myc transduction could significantly inhibit cell proliferation and induce cell apoptosis and G1-phase arrest in HLE B-3 cells. [PMID 15672251]
• p16INK4A, p14ARF, p53, and PCNA have roles in the progression of cervical neoplasia [PMID 15073118]
• p16 promoter hypermethylation is an important event in gastric carcinogenesis [PMID 18395906]
• Single nucleotide polymorphism in CDKN2A is associated with type 2 diabetes. [PMID 18991055]
• MTA1-mediated activation of ARF and ARF-mediated functional inhibition of MTA1 represent a p53-independent bidirectional autoregulatory mechanism in which these two opposites act in concert to regulate cell homeostasis and oncogenesis [PMID 21555589]
• Affinity Capture-Western [PMID 21555589]
• Hypermethylation of p16(INK4a)is associated with cervical carcinoma. [PMID 20112504]
• Senescent NHP cells that have lost progenitor markers and accumulated p16INK4a (p16) protein expression, appear to be the preferential fusion targets. Tumorigenicity of the NHP/293T-L hybrid cells was inhibited by exogenous p16 as well as hTERT. [PMID 18059027]
• CDKN2A loss is associated with diffuse large B-cell lymphomas. [PMID 20435884]
• Observational study of genetic testing. (HuGE Navigator) [PMID 21085193]
• Results show that p16 is consistently expressed in tubal metaplasia, less and only patchy expressed in the normal Fallopian tube, and is paralleled by aberrant expression of cell cycle proteins. [PMID 17429140]
• A method of detecting deletions in the INK4A gene is described in detail. [PMID 11692873]
• Hypermethylation of p14(ARF) is associated with primary adenocarcinomas of the small bowel [PMID 16619216]
• Evaluation of p16 and ESR1 promoter methylation in blood using real-time PCR appears to be very useful for lung cancer diagnosis [PMID 18949413]
• A fragment of the Hh-responsive GLI2 transcription factor directly binds and inhibits the p16 promoter and senescence is associated with the loss of nuclear GLI2. [PMID 21095584]
• The inactivation of the tumor suppressor gene p16 plays a role in the carcinogenesis of squamous cell carcinomas of the oral cavity, the pharynx and the larynx. There is no influence on the tumor dependent prognosis. [PMID 15197677]
• CDKN2A overexpression was associated with decreased event-free survival in meningiomas. [PMID 18374497]
• The most significant differentially expressed gene in HPV-related head and neck squamous cell carcinoma was CDKN2A [PMID 19795456]
• p16 methylation may have a role in the malignant transformation of gastric dysplasia [PMID 15297411]
• study identified aberrant p16INK4 expression in different stages of urothelial lesions; urothelial carcinoma in situ showed overexpression of p16INK4, suggesting a role of INK4a mutation as an early event of bladder carcinogenesis [PMID 18234280]
• P16 gene alteration may be associated with the development of some type of cervix neoplasms. [PMID 12911724]
• Increased protein expression of p16 and cyclin D1 in squamous cell carcinoma tissues. [PMID 20103831]
• Affinity Capture-MS [PMID 17955473]
• Affinity Capture-MS [PMID 17955473]
• Affinity Capture-MS [PMID 17955473]
• Affinity Capture-MS; Co-crystal Structure; Protein-peptide; Reconstituted Complex [PMID 17955473]
• Affinity Capture-MS [PMID 17955473]
• Affinity Capture-MS [PMID 17955473]
• Affinity Capture-MS [PMID 17955473]
• Affinity Capture-MS [PMID 17955473]
• Affinity Capture-MS [PMID 17955473]
• Affinity Capture-MS [PMID 17955473]
• Affinity Capture-MS [PMID 17955473]
• Affinity Capture-MS [PMID 17955473]
• Affinity Capture-MS [PMID 17955473]
• Affinity Capture-MS [PMID 17955473]
• Affinity Capture-MS [PMID 17955473]
• Affinity Capture-MS [PMID 17955473]
• Affinity Capture-MS [PMID 17955473]
• Affinity Capture-MS [PMID 17955473]
• Affinity Capture-MS [PMID 17955473]
• Affinity Capture-MS [PMID 17955473]
• Affinity Capture-MS [PMID 17955473]
• Affinity Capture-MS; Affinity Capture-Western [PMID 17955473]
• Affinity Capture-MS [PMID 17955473]
• Affinity Capture-MS; Affinity Capture-Western [PMID 17955473]
• Affinity Capture-MS [PMID 17955473]
• Affinity Capture-MS [PMID 17955473]
• Affinity Capture-MS [PMID 17955473]
• Affinity Capture-MS [PMID 17955473]
• Affinity Capture-MS [PMID 17955473]
• Affinity Capture-MS [PMID 17955473]
• Affinity Capture-MS [PMID 17955473]
• findings show that NSun2, a transfer RNA methyltransferase, inhibits the turnover of p16(INK4) mRNA; conclude that NSun2-mediated methylation of the p16 3’UTR is a novel mechanism to stabilize p16 mRNA [PMID 22395603]
• Detection of CDKN2A-MTAP co-deletion in peritoneal mesotheliomas can help identify those patients who may have an unfavorable outcome [PMID 20081810]
• mutations in sporadic and familial melanoma in the Polish population [PMID 12362978]
• These studies for the first time link Twist-1 to histone methylation of the Ink4A/Arf locus by controlling the expression of histone methyltransferases as well as the expression of other basic helix-loop-helix factors. [PMID 22290439]
• p16(INK4a) has low sensitivity but acceptable specificity for evaluation of low-grade cervical cytology smears harbouring high-grade lesions. [PMID 21614901]
• Loss of p16 protein is associated with gastrointestinal stromal tumors [PMID 15701851]
• Loss of p16/Rb protein (pRb) expression and overexpression of cyclin D1/CDK4 were observed in 49%/40% and 37%/37% of gastric carcinomas, respectively. [PMID 18484097]
• expression significantly correlated with biological behavior of oral squamous cell carcinoma [PMID 17052587]
• expression is predictive of better prognosis in colorectal adenocarcinoma in Tunisian patients [PMID 22095233]
• immunohistochemical expressions of cyclin D1, p16(INK4a) and Ki-67 were analyzed in a total of 127 cases showing multinucleated giant cells [PMID 21778791]
• P16 gene methylation and the expression of P16 protein were significantly different among the patients with different subclassification of gastrointestinal stromal tumors. [PMID 17659467]
• AUthors report a case of a family with melanoma presenting the splice site mutation g.193 G>C in p14/ARF exon 1[beta]. [PMID 19741424]
• the molecular mechanism of Bmi-1-mediated regulation of the p16 gene [PMID 20551323]
• Novel and recurrent p14 mutations in Italian familial melanoma [PMID 20132244]
• p14ARF-induced inhibition of MCF7 cell proliferation was significantly attenuated by downregulation of ATM by RNAi. [PMID 15258567]
• Results reveal a novel and direct role for p14ARF in the p53-independent maintenance of genomic stability. [PMID 19331830]
• PPARgamma promotes cellular senescence by inducing p16(INK4alpha) expression [PMID 18544633]
• Mutations in CDKN2A is associated with cutaneous malignant melanoma. [PMID 20574843]
• p16(INK4a) expression was regulated by the Polycomb group repressor Bmi-1, which is shown as a direct transcriptional target of c-Myc. [PMID 16537449]
• p16INK4a immunohistochemistry presented 31% sensitivity and 81% specificity for the diagnosis of anal squamous intraepithelial lesion (ASIL) and 30% and 66%, respectively, for the diagnosis of infection with high-risk HPV [PMID 21365778]
• A significant increase in p16(INK4A) and Bax expression was found in ulccerative colitis-associated tumors. [PMID 15292938]
• These findings uncover a feedback regulatory circuit in the astrocytic lineage and demonstrate tumor suppressor role for p18(INK4C) in human glioblastoma wherein it functions cooperatively with other INK4 family. [PMID 18394558]
• Transfer of the p16(INK4a) and p18(INK4c) genes and CDK4I suppressed the production of MMP-3 and MCP-1. [PMID 16802342]
• Cancerous tissues from 30 patients with HPSCC were examined for LOH in 4 tumor suppressor genes (TSGs) (p16, Rb, E-cadherin, and p53) at loci 9p21, 13q21, 6q22, and 17p13, respectively, using microsatellite markers amplified by polymerase chain reaction. [PMID 21493295]
• AP-1 heterodimers may contribute to the regulation of ARF expression upon oncogenic signaling [PMID 15688012]
• P16INK4a emerged with the most consistent correlations with age and histologic changes and inversely correlated with cell replication in kidney aging [PMID 14717921]
• p16 facilitates the movement of band 3 to plasma membrane with increased anion transport activity in 293t cells [PMID 15811326]
• We observed p16 (INK4A) immunolocalization in both the nucleus and the cytoplasm of a proportion of tumor cells [PMID 15223748]
• Inactivation of p21WAF1 sensitizes cells to apoptosis via an increase of both p14ARF and p53 levels and an alteration of the Bax/Bcl-2 ratio [PMID 12151395]
• p14ARF promotes accumulation of (H)Mdm2 conjugated to the small ubiquitin-like protein SUMO-1 [PMID 12297306]
• Induction of p16(INK4A) mediated by nuclear beta-catenin and p21(WAF1), along with loss of pRb expression, may be important for initial steps during trans-differentiation of Em Ca cells. [PMID 16858682]
• Data show that VentX is a direct transcriptional activator of p53-p21 and p16ink4a-Rb tumor suppression pathways. [PMID 21325273]
• Data show although detected at a higher frequency in primary effusion lymphoma cell lines than in primary primary effusion lymphoma tumors, TP53 and/or PTEN mutations, as well as deletion of CDKN2A-ARF locus are uncommon in primary effusion lymphoma. [PMID 19608668]
• Mutations and intragenic allelic losses in CDKN2A appear to play a role in the development of esophageal squamous cell carcinoma in high-risk Chinese populations. [PMID 14732922]
• CDKN2A inactivation played a significant role in the development of squamous cell carcinoma of the larynx [PMID 14991744]
• There is an association between the presence of HPV-16 in epithelial dysplasia and the occurrence of p16(CDKN2A) methylation. [PMID 22285991]
• HBx induces p53 expression through p14(ARF)-dependent and independent pathways to activate the p21(WAF1) promoter. [PMID 19726330]
• p16-Leiden gene is associated with increased risk of melanoma and pancreatic cancer. [PMID 18613292]
• We investigated the utility of a set of four independent genes (P16, TSHR, RASSF1A and RARbeta2) promoter hypermethylation analysis as a diagnostic or prognostic tool in papillary thyroid tumors [PMID 20535589]
• Loss of CDKN2A is associated with suppression of cyclin D1 gene expressions and malignant gliomas. [PMID 21843312]
• Abnormal expression of p16 gene then becomes involved in the development and metastasis of breast cancer. [PMID 11869517]
• There was a statistically significant association between p16 gene deletion and early stage, well differentiated bladder transitional cell carcinoma. [PMID 11869511]
• Hypermethylation of p14(ARF)is associated with cholangiocarcinoma. [PMID 22230750]
• Pathogenic mutations in CDKN2A nor exon 2 of CDK4 gene were not identified in uveal melanoma. [PMID 21412176]
• Polymorphism of p16 was not associated with the risk of epithelial ovarian cancer development and progression. [PMID 17466040]
• In diffuse large B cell lymphoma high levels of P16 may mitigate tumour cell prolifera-tion but gains of p16 do not necessarily increase P16 protein expression. [PMID 20332669]
• deletion in CDKN2 gene in melanoma patients is described [PMID 18298387]
• The combination of low expression of TS and induction of p16(INK4a) after chemotherapy can be important indicators of the sensitivity to 5-FU-based chemotherapy in colorectal cancers. [PMID 15260847]
• Study showed that deeper levels and ancillary staining with p16(Ink4a) and ProExC did not significantly reduce the discordance rate. [PMID 19521978]
• Results identify the point during neoplastic progression in epithelia when the tumor suppressor p16 and laminin 5 are expressed and suggest that normal epithelia may use the same mechanism to generate non-dividing, motile cells for wound repair. [PMID 12875969]
• the N-terminal region of the p14(ARF) protein is involved in binding to c-Myc and N-Myc proteins [PMID 17289033]
• Increased methylation of CDKN2A gene is associated with myelodysplastic syndromes and acute myeloid leukemia. [PMID 22248274]
• p16INK4a, RARbeta, and MGMT expression is activated by genistein and related soy isoflavones partially through a direct inhibition of DNA methyltransferase [PMID 16203797]
• A moderate overexpression of p14(ARF) with a normal expression of p16(INK4a) was observed in imatinib-resistant patients with chronic myeloid leukemia [PMID 16533530]
• Affinity Capture-Western [PMID 11297540]
• glucose restriction resulted in altered hTERT and p16 expression in response to epigenetic regulators in WI-38 rather than WI-38/S cells. [PMID 20019239]
• the tumor suppressor activity of ARF in melanoma-genesis is p53 independent [news] [PMID 17850505]
• Alteration of the p14(ARF)gene may play a role in early stage Japanese hepatocellular carcinoma carcinogenesis. . [PMID 15168247]
• Results show that p14/ARF is frequently involved in primitive neuroectodermal tumour (PNET) carcinogenesis, with a higher frequency, supratentorial PNET than for Medulloblastoma. [PMID 16623784]
• Observational study and meta-analysis of gene-disease association. (HuGE Navigator) [PMID 20490451]
• Aberrant methylation of hMLH1 and p16INK4a in Tunisian patients with sporadic colorectal adenocarcinoma [PMID 20815811]
• frequent and variable p14 gene abnormalities in glioma cell lines [PMID 18415661]
• Up-regulated p16 expression may represent a unique feature of aggressive neuroblastoma. [PMID 11705866]
• promoter hypermethylation of the p16, Runx3, MGMT, and DAPK genes may play an important role in the pathogenesis of gastric precancerous lesions and early gastric adenocarcinoma [PMID 19695681]
• The exon 2 region was required for physical binding of p14(ARF) to Topo I & stimulatory activity. p14(ARF) (R71A) was more efficient than wild-type to activate Topo I. Nucleolar location is linked the biological function of the ARF-Topo I complex. [PMID 12673200]
• p16 Hypermethylation in the early stage of hepatitis B virus-associated hepatocarcinogenesis. [PMID 12565176]
• Results suggest p16(INK4A) protein expression is an important predictive factor of lymph node metastasis in cervical carcinoma, and p16 overexpression is associated with a poor prognosis. [PMID 22011452]
• Incresed expression of p16(INK4a) and telomeres shortening were observed with age in some stem and progenitor cells. [PMID 18343732]
• Differential p16 and p53 expression in basaloid squamous cell carcinoma of esophagus suggests that these tumors are molecularly distinct from conventional esophageal squamous cell carcinomas. [PMID 19738459]
• Inacativaton of this cell cycle regulatory genes by DNA methylation could be associated with tumorigenesis in NK cell disorders. [PMID 15813917]
• The high frequency of methylation of the CDKN2A gene promoter suggests that the inactivation of tumor suppressor genes and of the genes related to the control of cellular proliferation through this mechanism is involved in gallbladder carcinogenesis. [PMID 16699861]
• aberrant methylation of p16 was observed in all of the stages, confirming that this epigenetic alteration is an early event during gastric carcinogenesis. [PMID 15859515]
• Results show that p14ARF associates with Brca1, which may play a major role in tumor suppression. [PMID 18703154]
• in addition to high-risk classification, p16 expression might be an indicator for "very high risk gastrointestinal stromal tumors." [PMID 18813351]
• Results allow the dissection of the "protein-protein binding" and "CDK4 inhibition" functions of P16, show that the difference between tumor suppressing and oncogenic functions of P16 and gankyrin, respectively, mainly resides in a single residue. [PMID 17881001]
• There may be a role for 3’ UTR polymorphisms in the CDKN2A gene in tumor invasiveness. [PMID 12532425]
• role of CDKN2A alleles in developing cutaneous melanoma (Review) [PMID 21051013]
• No p16 gene mutations were found in any cases of oropharngeal squamous cell carcinoma in this study. [PMID 14981901]
• our data suggest that methylation in the promoter region of the p14ARF gene may be used as a biomarker for the diagnosis of gliomas. [PMID 20714943]
• In colorectal tumors, nuclear expression of beta-catenin, p16 and c-myc was quantitatively increased from normal mucosa to premalignant adenoma, primary carcinoma and lymph node metastatic carcinoma. [PMID 14601048]
• Results suggest that silencing of p14ARF is involved in the pathogenesis of oesophageal adenocarcinoma and show that either DNA or histone methylation can provide the primary mechanism for ARF gene silencing. [PMID 18410530]
• CDKN2A CDKN2B and ANRIL is the susceptibility locus for coronary heart disease (CHD) and periodontitis. [PMID 19214202]
• Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator) [PMID 21048031]
• p16 interacts with CDK6. This interaction was modeled on a demonstrated interaction between human p16 and CDK6 from an unspecified species. [PMID 10491434]
• p16 interacts with CDK4. This interaction was modeled on a demonstrated interaction between human p16 and CDK4 from an unspecified species. [PMID 10491434]
• By epigenetic silencing of the p16INK4a gene, complete inactivation of the locus is achieved via ubiquitin-mediated protein degradation. [PMID 21200153]
• epigenetic inactivation of loci responsible for the regulation of cell division (p14ARF) and for segregation of chromosomes is associated with the occurrence of mosaic forms of the karyotype at early stages of human embryonic development. [PMID 19639877]
• a role for the p14ARF-Topo I complex in rRNA transcription and/or maturation. [PMID 15361825]
• Affinity Capture-Western [PMID 15361825]
• Hereditary p16-Leiden mutation in a patient with multiple head and neck tumors [PMID 12549483]
• Affinity Capture-Western [PMID 12640129]
• Expression of p16 was associated with better overall survival. [PMID 16273250]
• the genetic status of the CDKN2A-CDKN2B locus would be relevant in assessing patients with epidermotropic cutaneous T-cell lymphomas [PMID 20118908]
• These findings provide the first direct evidence that the p16(INK4a)/ARF/p15(INK4b) genetic region and the senescence machinery are active in physical ageing in heterogeneous human populations. [PMID 17459456]
• p16INK4A hypermethylation has a role in hepatocarcinogenesis from an early stage [PMID 15569978]
• Using pancreatic juice to detect mutations of p16 can help distinguish patients with pancreatic cancer from those without evidence of pancreatic neoplasia. [PMID 17106238]
• Tumor suppressor genes p15(INK4b), p14(ARF) and p16(INK4a) are located at the 9p21 locus in 26 cryopreserved neurofibromatosis type 1-related malignant peripheral nerve sheath tumors. [PMID 14519636]
• Cooperative effect of p21Cip1/WAF-1 and 14-3-3sigma on cell cycle arrest and apoptosis induction by p14ARF [PMID 18806827]
• inducible expression of p16(INK4a) sensitized a melanoma cell line to death induced by melphalan or actinomycin-D; study shows high expression of p16(INK4a) or the absence of activated B-RAF correlates with in vivo response of melanoma to cytotoxic drugs [PMID 18953432]
• study shows clear evidence of increased risk of cancers other than melanoma in CDKN2A families carrying the p16-Leiden mutation [PMID 18981015]
• Combined effects of cigarette smoke and hypermethylations of p16 are associated with non small cell lung cancer. [PMID 20704749]
• Frequent abnormalities of the p16 gene in mycosis fungoides and sezary syndrome. polymorphisms promoter methylation [PMID 11874489]
• Deletion analysis of p16(INKa) and p15(INKb) in relapsed childhood acute lymphoblastic leukemia. [PMID 12036898]
• Pathogenetic and biologic significance of TP14ARF alterations in nonsmall cell lung carcinoma. [PMID 12581892]
• Overexpression of p16INK4a can be used as an early marker of cervical cancer [PMID 11889694]
• Persistent hepatitis B infection may be associated with high rate of p16 methylation, and involved in development of hepatocellular carcinoma. [PMID 16649250]
• p16 plays an important role in cancer pathogenesis [PMID 18752124]
• Evidence of lymph node metastasis was significantly associated with negative p16 immunohistochemistry as well as with combined allelic loss and promoter hypermethylation in penile carcinoma [PMID 21085986]
• CDK4, MDM2, and p16 expression in the whorls suggests that they share a similar genetic background to well-differentiated [PMID 21317707]
• results demonstrate that early onset of senescence in omentum-derived human peritoneal mesothelial cells may be associated with oxidative stress-induced upregulation of p16INK4a [PMID 16254068]
• CDKN2A mutations /or deletions are not associated with gastric cancers. [PMID 20843112]
• Compared with the normal cerebellum, expression of p16 was significantly lower. Downregulation correlated with metastases, pathological type, necrosis, & differentiation level & direction. [PMID 19806481]
• The combination of RARB M4, INK4a/ARF, PRB, and HIN-1 CpG island promoter methylation may predict non-BRCA1/2-associated mammary carcinogenesis and tumor progression. [PMID 19258476]
• Strengthened signals in imputation-based analysis at CDKN2a SNP rs3731239 lends evidence to the role of cell cycle genes in ovarian cancer etiology. [PMID 19258477]
• for both p16(INK4a) and p14(ARF), promoter methylation is the commonest mechanism of gene inactivation. [PMID 15140233]
• Methylation of p16 was for the first time observed in retinoblastoma (9 tumors, 17%). [PMID 12391839]
• there appears to be a role for p16INK4a gene promoter hypermethylation in dedifferentiated liposarcomas and not in recurrent well-differentiated liposarcoma . [PMID 19186005]
• Aberrations of the p14(ARF) and p16(INK4a) genes in renal cell carcinomas [PMID 11749694]
• Both P16 and CDH1 had different expression levels in tumor tissues compared to the adjacent normal tissues. [PMID 20568901]
• p16 hypermethylation may be a frequent genetic aberration in multiple myeloma. [PMID 16541270]
• Activation of ERK together with its downstream transcriptional machinery mediated p16(INK4a) expression that led to HepG2 growth inhibition triggered by TPA and Saikosaponin a. [PMID 12592382]
• Promoter hypermethylation of p16 is frequent in gastric cancer and may be an important help in evaluating the differentiation grade and lymph node status of gastric cancer. [PMID 21302620]
• CDKN2A/ARF, RAS and TP53, but not BRAF, PTEN, MAPK2 or EGFR may have roles in rare salivary gland tumours [PMID 21503581]
• regulation of p16, p21, p27 and c-myc is increased by oridonin, which induces apoptosis and senescence in colorectal cancer cells [PMID 21054888]
• There is a role for caveolin-1 in degenerative rather than age-induced changes in the nucleus pulposus. A positive correlation was identified between gene expression of caveolin-1 and p16INK4a (biomarker of cellular senescence). [PMID 18681962]
• CDKN2a mutations are unlikely to predispose pancreatic cancer in familial pancreatic cancer families without melanoma [PMID 20195775]
• Findings indicate correlation between the increased expression of p16 during the progression of skin from actinic keratosis to in situ squamous cell carcinoma to invasive squamous cell carcinoma. [PMID 12429789]
• Affinity Capture-MS [PMID 16449650]
• p16(INK4A) and p27(Kip1) are key targets in the Atr-dependent signaling pathway in response to UV damage. [PMID 21270107]
• p16 was lacking in the malignant rhabdoid tumor of the liver. [PMID 15796965]
• Aberrant methylation of the p16 gene may be a useful indicator of the potential malignancy of epithelial cells of the pancreas. [PMID 12000709]
• INK4a/ARF promoter hypermethylation may serve as a marker of global methylation dysregulation. [PMID 18006786]
• Studies indicate that senescence occurs with the inactivation of suppressor elements leading to the enhanced expression of p16. [PMID 22025288]
• Studies identify a novel link between wood smoke expodure and gene promotor methylation of the p16 and GATA4 genes that synergistically increases the risk for reduced lung function in cigarette smokers. [PMID 20595226]
• Aberrant methylation of multiple genes (E-cadherin, estrogen receptor, RB1 , p16, p15, p14, and MGMT) is involved in gastric carcinogenesis. [PMID 17652530]
• The results unveil a backup tumor suppressor role for p16(Ink4a) in the event of p53 inactivation, expanding our understanding of how p16(Ink4a) expression is regulated in vivo. [PMID 19667129]
• Differential p16 patterns by interphase cytogenetics in malignant peripheral nerve sheath tumor and morphologically similar spindle cell neoplasms. [PMID 12152785]
• Abrogation of the p16 is associated with head and neck squamous cell carcinomas [PMID 17549378]
• p16 controls the cell cycle as tumor suppressor [PMID 20861610]
• Upregulation of p14ARF paralleled with MDM2 inhibition contributes to p53 accumulation in the nucleus in radiation-treated breast cancer cells. [PMID 14729628]
• p16INK4a and p14ARF aberrations are common in oral verrucous leukoplakia. Loss of heterozygosity occured in 45% of PVL patients. [PMID 18990760]
• study shows that p14ARF directly associates with Myc and relocates Myc from the nucleoplasm to the nucleolus, in addition, p14ARF down regulates Myc activated transcription [PMID 16410719]
• Germ line polymorphisms in the folate- and methyl-associated genes MTHFR, MTR and MTRR, were analyzed in colorectal cancer patient cohort to find a possible link between these genetic variants and p16 hypermethylation. [PMID 20549016]
• MEOX2-induced senescence is dependent upon INK4a activity, and chromatin immunoprecipitation studies indicate that MEOX2 directly binds the INK4a promoter [PMID 19340300]
• The results show that the LOH pattern in genes p16 and p14ARF occur as well in leuplakia with malignant transformation as in leukoplakia, that do not show clinical alterations. The rate of allelic loss did not differ significantly. [PMID 17990010]
• p16INK4a expression in cervical preneoplastic and neoplastic lesions and correlation with lesion grade [PMID 16257403]
• expression status is an independent prognostic factor in non-small cell lung cancer; meta-analysis [PMID 21621871]
• p16(INK4a)/Rb-induced telomere-independent senescence [PMID 16767161]
• Mutations within the CDKN2A gene are associated with risk of melanoma development. [PMID 21325014]
• Affinity Capture-Western [PMID 22383580]
• The interaction of p14(ARF) with mitochondrial proteins, including p32 and enables p53-independent cell death. [PMID 20107316]
• Increased p16/CDKN2A staining is strongly associated with high-grade squamous neoplasia in anal intraepithelial neoplasia. [PMID 20871219]
• the analysis of p21cip1, p27kip1, and p16INk4a by immunohistochemistry could be useful in the management of patients with papillary thyroid carcinoma [PMID 18766473]
• We propose that a cellular stress related to the amplified CTG repeat promotes premature senescence mediated by a p16-dependent pathway in myotonic dystrophy type 1 muscle precursor cells. [PMID 19246640]
• The frequency of p16INK4A or CDH13 hypermethylation in patient serum and the total lack of methylation in serum from healthy individuals, offer a promising tool for non invasive early detection of lung cancer. [PMID 16222700]
• cytoplasmic p16 bound cyclin dependent kinase (cdk)4/6, potentially indicating that p16 could have a function in the cytoplasm [PMID 16161044]
• aberrant methylation is more frequent in invasive lung adenocarcinomas than in noninvasive tumors [PMID 19144441]
• EBV infection and p16 alteration are two independent roles in gastric adenocarcinomas carcinogenesis. [PMID 19105332]
• high-risk human papillomaviruses were involved in inducing p16 and hTERT overexpression in Bowenoid papulosis [PMID 16919029]
• The present study has shown a high prevalence of CDKN2A mutations affecting p16INK4A in Slovenian population of familial melanoma patients [PMID 18803811]
• p16 is a highly sensitive marker for cervical epithelial dysplasia. [PMID 17543474]
• The expressions of p16, Ki-67, and L1 proteins and human papillomavirus DNA were investigated as potential molecular markers for the diagnosis and transforming potential of low cervical intraepithelial neoplasia [PMID 21979598]
• Affinity Capture-MS; Affinity Capture-Western; Reconstituted Complex [PMID 18259216]
• Results define a mechanism by which the ARF tumor suppressor targets the translational repression of specific oncogenes during neoplastic transformation. [PMID 20501856]
• Alteration of p16 gene alone or in combination with alterations of other tumor suppressor genes on chromosome 9p is a prognostic indicator in gallbladder carcinoma. [PMID 15014024]
• Ablation of either USP7 or USP11 in primary human fibroblasts results in de-repression of the INK4a tumour suppressor accompanied by loss of Polycomb repressive complex 1 binding at the locus and a senescence-like proliferative arrest. [PMID 20601937]
• The morphology and cell cycle proteins immunoexpression of the novel probable preinvasive lesion - bronchiolar columnar cell dysplasia (BCCD), is decribed. [PMID 18296270]
• close correlation between inactivation of p16 gene and gastric carcinoma [PMID 12717828]
• reduced expression of pl6 is a common event in pheochromocytomas, and the primary cause for such downregulation is inactivating genetic abnormalities in the p16 gene [PMID 19110720]
• p16(INK4a) contributes to the p53-independent response to telomere damage. [PMID 15620660]
• degree expression is related to the histological type of tumor but not to the histological indicators of tumor invasiveness and that intragenic mutations and promoter hypermethylation are not major mechanisms of p16 inactivation in sporadic uveal melanoma [PMID 12362979]
• Affinity Capture-MS [PMID 20360068]
• Expression may be reduced in some early gastric carcinomas. [PMID 17671701]
• p14(ARF)-induced apoptosis in p53 protein-deficient cells is mediated by BH3-only protein-independent derepression of Bak protein through down-regulation of Mcl-1 and Bcl-xL proteins [PMID 22354970]
• Methylation of the promoter region of the p16 gene in patients with stage I NSCLC treated with curative intent by means of surgery is associated with early recurrence. [PMID 18337602]
• HPV-positive squamous cell carcinoma tumours of the vagina were more frequently of non-keratinizing, basaloid or warty type than HPV-negative neoplasms (84% versus 14.3%; P<0.001), and showed diffuse positive immunoreactivity for p16(INK4a) [PMID 21166704]
• Losses of INK4a/INK4b gene products play a big role in meningioma formation & malignant progression. Inactivation of p16/p15 and pl4ARF pendent pathways possibly along with telomerase activation might be critical for meningioma immortalization. [PMID 11859969]
• P16 protein has a prognostic value in assessment of disease free survival [PMID 18546941]
• The patients with emphysema had significantly higher percentages of type II cells positive for p16INK4a and p21CIP1/WAF1/Sdi1 than the asymptomatic smokers and nonsmokers. [PMID 16888288]
• inhibits Plasmodium falciparum cyclin dependent protein kinases [PMID 11700040]
• accumulation of nevi in mutation carriers supports a nevogenic role for this CDKN2A mutation. [PMID 15304099]
• there is an association between PPARG, KCNJ11, CDKAL1, CDKN2A-CDKN2B, IDE-KIF11-HHEX, IGF2BP2 and SLC30A8 and type 2 diabetes in the Chinese population [PMID 19862325]
• over-expression of human OVCA1 in ovarian cancer cells leads to up-regulation of p16 [PMID 21487939]
• The association of p16 gene methylation in head and neck squamous cell carcinoma with smoking, family history and survival is depedent on age. [PMID 20514408]
• BMI-1 mediated repression of p16(ink4a) may contribute to an increased aggressive behavior of stem cell-like melanoma cells. [PMID 17597110]
• Variants are associated with multiple primary cutaneous melanomas in a Norwegian population. [PMID 18023021]
• Only p16 (INK4A )and TIMP3 were methylated consistently in medulloblastomas (p16 (INK4A ) 14%, TIMP3 11%) and p16 (INK4A) also in anaplastic ependymomas (1/4 tumors). [PMID 17206475]
• The stabilization effect exerted by TBP-1 requires an intact N-terminal 39 amino acids in ARF and occurs independently from N-terminal ubiquitination of the protein. [PMID 17334400]
• Affinity Capture-Western; Two-hybrid [PMID 17334400]
• MDM2-p73-P14ARF pathway is involved in the progression of bladder cancer to a more malignant and aggressive form. [PMID 15492852]
• Suggests that the long dual coding region and/or the resulting disordered protein structure may facilitate NMD escape of the variant encoding the p14ARF isoform. [PMID 20212158]
• CDKN2A appears to be a low penetrance breast cancer susceptibility gene in Poland [PMID 15879498]
• These genetic and translational observations establish a cooperative role of Pten and Ink4a/Arf in the development of HS and provide mechanistic insights into the pathogenesis of human HS. [PMID 16697958]
• Loss of p16Ink4a by promoter hypermethylation is associated with lung adenocarcinoma. [PMID 21164364]
• The assessment of p16, EGFR, and COX-2 allows to an integrative approach for the progression of squamous intraepithelial lesion, associated or not with the human papilloma virus infection. [PMID 22203921]
• Different mechanisms of CDKN2A deletion prevail in different human cancers. [PMID 15495191]
• Regarding CDKN2A and Snk/Plk2 CpG island methylation analysis, we found 12 of 45 multiple myeloma patients and 27 of 45, respectively, to be methylated. [PMID 21067440]
• Loss of p16(INK4A) expression may be a pathogenetic factor in the progression from serous borderline ovarian tumors to low-grade invasive carcinomas. [PMID 21131838]
• Nuclear p16 expression is absent in normal gallbladder epithelium and is a frequent event in high-grade dysplasia of the gallbladder and gallbladder adenocarcinoma. [PMID 18486890]
• Correlation of p16/INK4a gene damages and protein expression in the tumor tissue of sporadic breast cancer [PMID 18807517]
• ARF induces the ATR- and Chk1-dependent phosphorylation of the RelA transactivation domain at threonine 505, a site required for ARF-dependent repression of RelA transcriptional activity. [PMID 15775976]
• These data provide further evidence for a pancreatic cancer-melanoma syndrome associated with CDKN2A germline mutations affecting p16. [PMID 12454511]
• overexpression of p16INK4A and p14ARF act as potential biomarkers for cervical cancer progression from premalignant lesions. [PMID 15502810]
• nucleolar localization determines the stability of ARF but not its primary function [PMID 17968318]
• From genetic analysis of 31 female patients in Spain, germline mutations in CDKN2A are infrequent in patients with cutaneous melanoma and breast cancer. [PMID 19571771]
• Down-regulated p16 expression predicts poor prognosis in patients with extrahepatic biliary tract carcinomas [PMID 11836554]
• study presents a novel functional interaction of p16 and K-Ras. Re-expression of the tumor suppressor in pancreatic cancer cells restricted Ras oncoprotein activity, which resulted in loss or reduction of their transforming potential [PMID 22049925]
• the molecular basis of the ARF-B23 interaction [PMID 16679321]
• Can initiate a cyclin-dependent kinase (CDK)4- or CDK6-dependent autonomous senescence program that is disabled by inherited melanoma-associated mutations. [PMID 18843795]
• relationships between familial melanoma, pancreatic cancer and germline CDKN2A mutations using published data to determine whether any identifiable patterns exist [PMID 15146471]
• Epigenetic regulation of the INK4b-ARF-INK4a locus: in sickness and in health. [PMID 20716961]
• Loss of p16 is associated with lung cancer. [PMID 20237870]
• We could detect colorectal cancer related genetic alterations by analyzing stool DNA with a sensitivity of 64% and 20% and a specificity of 95% and 100% for Long DNA and p16 respectively. [PMID 17461444]
• positive expression rate and co-expression rate of P21WAF1/CIP1 and P16 proteins could reflect the malignant grade of glioma to some extent, and they can be considered as a sensitive index for glioma grading [PMID 18791688]
• p16INK4a hypermethylation is associated with hepatocellular carcinoma [PMID 18358501]
• p16(INK4a) plays a role in maintaining homeostasis during erythroid differentiation. [PMID 12763133]
• haplotypes in NBN and XRCC4, and CDKN2A were associated with structural and numerical change subtypes, respectively, in childhood acute lymphoblastic leukemia [PMID 21987080]
• association of p14ARF with the p120E4F transcriptional repressor enhances cell cycle inhibition [PMID 12446718]
• Affinity Capture-Western; Two-hybrid [PMID 12446718]
• Immunostaining with p16 should be considered as a highly desirable addition to the histologic evaluation of cervical biopsy specimens in high-risk human papillomavirus positive women. [PMID 19047902]
• Inactivation of p16 is associated with malignant transformation, contributing to a differentiation defect [PMID 17292825]
• p16(INK4a) expression in peripheral blood T-cells is an easily measured, peripheral blood biomarker of molecular age. [PMID 19485966]
• Affinity Capture-Western [PMID 12606707]
• The data delineate the pathway by which ARF regulates ribosomal RNA synthesis and provide a compelling explanation for the role of NPM. [PMID 20513429]
• Affinity Capture-Western [PMID 14612427]
• in bronchial squamous cell carcinoma, p14arf (cyclin-dependent kinase inhibitor 2A) expression loss or its nucleolar relocalisation both increased at severe dysplasia;nucleolar relocalisation of p14arf was associated with that of Nucleoplasmin [PMID 18480108]
• ARF pathway is required for the elimination of cells with aberrant CD43 expression. [PMID 17891181]
• Results indicate that both p16(INK4a) and p21(WAF1/CIP1) are required for the opioid growth factor (OGF)-OGF receptor axis to inhibit cell proliferation in normal cells. [PMID 18923142]
• loss of expression of CDKN2A via deletion plays an important role in the pathogenesis of human NMSC. Deletions in CDKN2A could arise spontaneously, perhaps during tumour progression. [PMID 18070208]
• JMJD3 is recruited to the INK4A-ARF locus and contributes to the transcriptional activation of p16INK4A in human diploid fibroblasts [PMID 19451217]
• p16( INK4a) is also a modulator of transcription and apoptosis through controlling the expression of two major transcription regulators, AUF1 and E2F1 [PMID 21799732]
• Analysis of the p16 gene status of non-familial dysplastic nevus syndrome patients. [PMID 11820732]
• p14ARF interacts with HIF-1alpha. [PMID 11382768]
• the anti-cancer effect of p16 is modulated by p16-mediated cell cycle arrest and by the induction of senescence [PMID 12883667]
• p16 FISH is a more sensitive and specific test than GLUT-1 immunohistochemical analysis and can be a more reliable ancillary tool to support the diagnosis of mesothelioma. [PMID 21411785]
• Observational study of genotype prevalence. (HuGE Navigator) [PMID 17624602]
• p16(INK4a) overexpression was common and was a marker of favorable prognosis. p16(INK4a) overexpression was not a reliable predictor of HPV positivity in our cohort of oral tongue squamous cell cancer patients. [PMID 21990227]
• Cigarette smoking is positively correlated to p16(INK4alpha) gene hypermethylation in non-small cell lung carcinoma patients. [PMID 22174919]
• In summary, the p53/p21 pathway is mainly responsible for GC-induced apoptosis, but the coordinated activation of the p53/p21 and p16 pathway is responsible for GC-induced endothelial cell senescence through a Rb-dependent mechanism. [PMID 16243918]
• p16INK4a and Fhit expression is altered in carcinogenesis and progression of human oral cancer [PMID 14719099]
• deletion in the INK4a/ARF locus might contribute to tumor progression in renal cell carcinoma at least partly by functional inactivation of wild-type p53 [PMID 17201148]
• Immunoexpression of p16INK4,absent Skp2, low mitotic index and Ki67 indicates that p16INK4 is responsible for cell cycle arrest. [PMID 21151393]
• Numerical aberrations of chromosome 9 and p16 gene deletion are common findings in all subtypes of non-small cell lung cancer. [PMID 20032395]
• Expression of DNMT3B was inversely correlated with that of p14ARF and p16INK4a. Results suggest that DNMT3B over-expression may be involved in the suppression or lower expression of p14ARF and p16INK4a observed in esophageal squamous cell carcinoma. [PMID 17017004]
• rs4977756, a genetic variant of CDKN2A and CDKN2B, was one of 3 genetic variants implicated in a pool of US epidemiologic studies of glioma risk [PMID 21920947]
• large or smaller deletions of the CDKN2A locus underlie the CDKN2A/p16 protein expression loss in some conventional osteosarcomas and might be a plausible explanation for the rapid proliferation and high aggressiveness of these osteosarcomas [PMID 20737480]
• The overall rate of deleterious CDKN2A mutations in the familial melanoma pedigrees, even though the sample size is small, was considerably higher (83%) than the often quoted range. [PMID 19523171]
• Expression of p16(INK4) correlated with the survival time. Its loss was significantly associated with osteopontin overexpression. Patients with osteopontin (-) and with p16(INK4) (+) lived longer than patients with osteopontin (+) and with p16(INK4) (-). [PMID 19813107]
• it is concluded that mutation of p53 & deletion of p16 might play important roles in the tumorigenesis of gliomas [PMID 16696307]
• in colorectal carcinoma patients, the p16 methylation score significantly increased with tumor stage; the p16 methylation score was significantly higher in patients with lymph node metastasis and tumor invasion to the veins [PMID 17970082]
• Immunostaining for p16 showed moderate to strong diffuse immunoreactivity in 11/13 cases (84.6%) of atypical leiomyomas [PMID 19851199]
• Meta-analysis and genome-wide association study of gene-disease association. (HuGE Navigator) [PMID 17463249]
• Aberrant promoter hypermethylation of p16 gene is associated with oral squamous cell carcinomas [PMID 16791592]
• Promoter hypermethylation and the 540 C>T polymorphism of CDKN2A in cutaneous melanoma of the vertical growth phase. (P = 0.025). Point mutations in CDKN2A were found in 4%; 90% had loss of heterozygosity at one or more of 4 markers. [PMID 12107107]
• There is more frequent p16 hypermethylation in mantle cell lymphoma and p15 or Rb1 hypermethylation in follicular lymphoma. [PMID 17900658]
• CDKN2A can be implicated in the carcinogenesis process of only a subset of gastric neoplasias. [PMID 18622497]
• The combination of L1 capsid protein and p16 appears to be useful for an early diagnosis and may be able to identify the patients with risk of lesion progression. [PMID 20809026]
• p16(INK4a) lesions are common, early abnormalities that undergo clonal expansion in Barrett’s metaplastic epithelium [PMID 11719461]
• Evaluation of 3 different scoring mechanisms of p16INK4a immunohistochemical staining in distinguishing between endometrial and endocerviccal adenocarcinoma. [PMID 19366452]
• Analysis of p16INK4a expression in aggressive fibromatosis (desmoid tumor) is reported. [PMID 19130399]
• Promoter methylation of cyclin-Dependent Kinase Inhibitor p16 is associated with malignant fibrous histiocytomas [PMID 17094467]
• Study shows that the ability of the oncogene BMI1 to repress the INK4A-ARF locus requires its direct association and is dependent on the continued presence of the EZH2-containing Polycomb-Repressive Complex 2 complex. [PMID 17344414]
• p14(ARF) hypermethylation and MGMT hypermethylation constitute distinct molecular pathways of astrocytoma progression, which could differ in biological behavior and clinical outcome. [PMID 17493032]
• Abolition of p21(Cip1/Waf1) and p16(Ink4a) functions prevented oncogenically activated Ras from inducing growth arrest and was sufficient for limited anchorage-independent growth but not tumorigenesis. [PMID 12665584]
• aberrant expression of Cdc6 is oncogenic by directly repressing the INK4/ARF locus through the RD(INK4/ARF) element [PMID 16572177]
• This study provides evidence that obesity and occupational exposure increase the risk of developing esophageal cancer through an enhancement of CDKN2A/p16 promoter methylation. [PMID 20459442]
• but also in a significant fraction of atypical hyperplasia and in situ carcinomas. P16(INK4a) methylation and gamma-tubulin gene amplification had a synergistic effect on tumor progression. [PMID 19131428]
• whereas wild type p16INK4a strongly inhibits NF-kappaB transcriptional activity, a subset of melanoma-associated p16INK4a mutants show reduced NF-kappaB inhibitory function [PMID 15913553]
• Human papillomavirus-infected esophageal squamous papillomas show low expression of cell-cycle markers (p16, p53). [PMID 19084918]
• We investigated methylation patterns in the promoter regions of ABCB1, ATM, BRCA1, CDH3, CDKN2A, CXCR4, ESR1, FBXW7, FOXC1, GSTP1, IGF2, HMLH1, PPP2R2B, and PTEN75 in well-described pre-treatment samples from locally advanced breast cancer [PMID 20338046]
• Deletion rate was 25/54 (46%), of these 19/25 (76%) were homozygous. Small deletions (<200 kb) were found in 8/25 (32%) and the smallest deletion was <30 kb. [PMID 18328560]
• alterations of the INK4a-ARF locus are frequent and important events not only in the carcinogenesis of malignant, but also in benign tumors. [PMID 12924439]
• p16 overexpression was noted in the carcinomatous component in 96.7%, and in the sarcomatous component in 86.7% of cases of uterine malignant mixed mullerian tumors [PMID 19851197]
• Inactivation of tumor suppressor genes p15(INK4b) and p16(INK4a) in primary cutaneous B cell lymphoma. [PMID 12060387]
• This study demonstrates that p16(INK4a) is not a useful surrogate marker for HPV detection across the various Schneiderian papillomas. [PMID 20405251]
• Hypermethylation of E-cadherin, p14 or RASSF1A in urine sediment DNA is a potential biomarker for detecting superficial, low grade cancer [PMID 19181545]
• Immunohistochemical trio of CDK4, MDM2, and p16 is a useful ancillary diagnostic tool that provides strong support in distinguishing well-differentiated/dedifferentiated liposarcomas from other adipocytic neoplasms. [PMID 22301498]
• p16(INK4A) promoter methylation in melanoma was significantly overrepresented in NRAS-mutated samples compared to NRAS wild-type samples (P=0.0004), indicating an association between these two events [PMID 20703244]
• P16 gene silencing by hypermethylation is more common in null cell adenomas. The role of p16 in the pathogenesis of pituitary adenomas is restricted to specific tumor subtypes. [PMID 11740049]
• Prognostic significance of p16INK4a alterations and 9p21 loss of heterozygosity in locally advanced laryngeal squamous cell carcinoma. [PMID 12124774]
• p16 is expressed in cutaneous squamous cell carcinomas [PMID 16989737]
• Results suggest that methylation is the predominant mechanism of inactivation of the CDKN2A in ESCC. [PMID 17970080]
• Hypermethylation and protein expression of p16 INK4A is associated with uterine cervical lesions [PMID 15785933]
• Telomere dysfunction and inactivation of the p16(INK4a) pathway might play a role for pyrothorax-associated lymphoma [PMID 17428253]
• p14(Arf) and HMGA2 seem to play a pivotal role in controlling the growth of fibroid cells. [PMID 21498692]
• results suggested that p16 hypermethylation was associated with early incidence of oral squamous cell carcinoma, increased lymph node invasion in young patients, and poor prognosis in older patients. [PMID 20729138]
• Cervical brush samples allow an unequivocal cytohistodiagnosis based on the (pre)malignant nuclear changes highlighted by the p16 staining of the paraffin sections. [PMID 19365965]
• p16(INK4a), p21(WAF1/CIP1), p27(KIP1), and p53 are expressed in human corneal endothelial cells despite donor ages. [PMID 18334933]
• Higher expression of p16INK4A is associated with improved radiotherapy treatment response and survival in squamous cell carcinoma of the head and neck infected with HPV. [PMID 19289615]
• p16INK4A was downregulated both in retinoblastoma patients and their parents suggestsing that this alteration could be a novel inheritable susceptibility marker to retinoblastoma. [PMID 20039270]
• Report roles of p16(INK4A) and p21(WAF1) in replicative senescence and ionizing radiation-induced accelerated senescence in human normal, ataxia telangiectasia and Li-Fraumeni syndrome fibroblast strains. [PMID 20039273]
• Promoter methylation of p14ARF may be an important mechanism in oral squamous cell carcinoma (OSCC), and its determination may be considered an important tool in the early diagnosis and treatment of OSCC. [PMID 20586029]
• Data suggest that the region spanning -62 to +1 bp of p16(INK4a) promoter plays a role in p16(INK4a) transcription regulation. [PMID 17333389]
• Results suggest that CDKN2A may be haploinsufficient in human cancer. [PMID 16115911]
• Association study of common variation spanning the CDKN2A/CDKN2B locus confirms the strong association between the distal susceptibility variant and type 2 diabetes in the French population. [PMID 18368387]
• Lower expression of p16 protein and overexpression of Cyclin D1 protein may be considered as prognostic biomarkers to skin carcinogenesis. [PMID 11860939]
• heterogeneous RB (pRb2 or p16) and p53 (p53, p14, or p21) pathway alterations occur frequently in Burkitt lymphoma [PMID 21127431]
• p16 appears not to be directly involved in the development of sinonasal or urothelial inverted papilloma. [PMID 18334838]
• DNA methylation in CDKN2A associated to the MTHFR 677T carrier is suggested to be a distal tumor characteristic, especially in those 60 years old or older, and it seems to depend on the infection by H. pylori cagA/vacAs1m1 strains. [PMID 20957490]
• Study shows the pivotal roles of Dmp1 in HER2/neu-p53 signaling and breast carcinogenesis. [PMID 21062982]
• Six SNP(rs7754840 in CDKAL1, rs391300 in SRR, rs2383208 in CDKN2A/2B, rs4402960 in IGF2BP2, rs10830963 in MTNR1B, rs4607517 in GCK)risk alleles of type 2 diabetes were associated with GDM in pregnant Chinese women. [PMID 22096510]
• Stresses and stimuli that reduce CtBP-mediated repression are associated with increased p16 expression; therefore, CtBP may provide a common final target for regulating the balance among tumor suppression, regenerative capacity, and senescence [PMID 18676825]
• Down-regulation of p16/INK4a expression and promoter hypermethylation of the p16/INK4a gene is associated with ocular adnexal lymphomas. [PMID 19728399]
• Binding of ARF to DP1 results in an inhibition of the interaction between DP1 and E2F1 and the G1 arrest. [PMID 16135794]
• Low expression of p16 was detected but had no effect on survival or recurrence in the univariate analysis. [PMID 17611661]
• Studies indicate that p53, arf and other tumor suppressors might be barriers to reprogramming somatic cells for the generation of induced pluripotent stem cells. [PMID 19801173]
• Suggest p16 overexpression cannot be used as a surrogate maker for human papilloma virus infections in high-grade adenoid cystic carcinoma of the head and neck. [PMID 22157933]
• Reduction of levels of p21Cip1 and p16INK4a could be useful in development of treatments to induce transient cell division to increase corneal endothelial cell density. [PMID 20508865]
• Single nucleotide polymorphisms in p16, RB1 genes may affect the susceptibility to cervical cancer collectively. [PMID 21567202]
• Although p16 was not found to have prognostic significance in serous papillary endometrial carcinoma, it may be valuable as a diagnostic adjunct in histologically ambiguous tumors. [PMID 22027748]
• Data show that overexpression of p33(ING1b) induces cellular senescence and upregulates p16(INK4a) expression in fibroblasts. [PMID 21896275]
• YY1, HDAC3 and HDAC4 restrained cell senescence by repressing p16(INK4a) expression through an epigenetic modification of histones [PMID 18558095]
• RB1CC1 activates the expression of p16 (also called INK4a/CDKN2a) through the activation of its promoter. RB1CC1 essentially requires binding with hSNF5 to activate the p16 promoter. [PMID 21637919]
• results suggest that p16INK4a overexpression is independent of human papillomavirus infection in lobular endocervical glandular hyperplasia [PMID 16633071]
• Data suggest that p16INK4a plays a principal role in Ras-induced growth arrest in human fibroblasts. [PMID 12417717]
• uncommon coexistence of a germline mutation in two suppressor genes, RET and CDKN2A in multiple endocrine neoplasia 2a [PMID 18299477]
• In patients with ulcerative colitis, hypermethylation of p14 ( ARF ) seems to be associated with an early stage of dysplasia. [PMID 17665255]
• results suggest that p16 suppresses MMP-2 by blocking Sp1-mediated gene transcription [PMID 16575904]
• There is an increased melanocytic nevi and nevus density in a G-34T CDKN2A/p16 melanoma-prone pedigree. [PMID 18337833]
• Hypertension induces cellular senescence via p16(INK4a), possibly through p38, thereby contributing to hypertensive target organ damage. [PMID 18504326]
• Hypermethylation of both p16 and APC strongly predicts progression to high-grade dysplasia or cancer in patients with Barrett’s esophagus. Absence of p16 and APC hypermethylation is associated with a benign course. [PMID 19584833]
• in tumor cells lacking functional p53 and/or p21, p14(ARF) impaired mitotic entry and enforced a primarily cytoplasmic localization of p34(cdc2) that was associated with a decrease in p34(cdc2) kinase activity and reduced p34(cdc2) protein expression [PMID 15582998]
• BRAF(V600E) mutation seems to define a subset of malignant astrocytomas in children, in which there is frequent concomitant homozygous deletion of CDKN2A (five of seven cases). [PMID 20068183]
• ARF interacts with MDM2 in the nucleoplasm but is consequently subject to proteasomal degradation [PMID 15286709]
• that the tumor suppressor p16 may exert its antitumor effects through modulation of multiple aspects of glioblastoma phenotypes, including proliferation, invasiveness, and responsiveness to extracellular growth stimuli. [PMID 11908877]
• these findings provide the first demonstration that SM22alpha modulates cellular senescence caused by damaging agents via regulation of the p16(INK4a)/pRB pathway in HepG2 cells and that these effects of SM22alpha are partially mediated by MT-1G. [PMID 20705054]
• The mutation creates a false GT splice donor site 105 bases 5’ of exon 3 and has been demonstrated to result in aberrant splicing of the mRNA. [PMID 11726555]
• These results demonstrate that the MAPK ERK signaling pathway contributes to the p53-independent antiproliferative functions of p14ARF. Furthermore, they identify a new mechanism by which phosphorylation at serine 216 participates to Cdc25C inactivation. [PMID 16582626]
• Study identified driver mutations in three known pancreatic cancer driver genes P53, SMAD4 and CDKN2A. [PMID 20581473]
• high laminin gamma2 mRNA and protein expression in their basement membranes were associated with long nerve invasion in tumors of pancreatic cancer. [PMID 20013810]
• a carrier of the founder CDKN2A [p.Leu113Leu;p.Pro114Ser] mutation as well as two MC1R moderate-risk variants, [p.Arg151Cys(+)p.Arg163Gln] developed 22 primary melanomas in the 3 years that followed initiation of levodopa therapy for Parkinson’s disease [PMID 17492760]
• results suggest that mutation of p16/CDKN2 gene was a common factor in development of malignant mucosal melanomas & adenoid cystic carcinomas [PMID 17912431]
• Nine patients had p16 mutations within the Barrett’s epithelium. [PMID 16551852]
• Cooperation of CREG1 and p16 (INK4a) inhibits the expression of cyclin A and cyclin B by inhibiting promoter activity thereby decreasing mRNA and protein levels; these proteins are required for S-phase entry and G2/M transition. [PMID 21263217]
• Results indicate that in Chinese Hans, common variants in CDKN2A loci independently or additively contribute to type 2 diabetes risk, likely mediated through beta-cell dysfunction. [PMID 18633108]
• High p16 expression is associated with positive response to chemoradiotherapy in stage IVa/b head and neck squamous cell carcinoma [PMID 21627359]
• Magnetic resonance imaging is able to detect small solid pancreatic tumors in p16-Leiden mutation carriers as well as small possible precursor lesions. [PMID 21129377]
• Genetic polymorphisms in p14ARF may have an impact on the risk of chronic benzene poisoning in a Chinese worker population. [PMID 19596022]
• Wip1 overexpression abrogates the homeostatic balance maintained through the p38-p53-Wip1 pathway, and contributes to malignant progression by inactivating wild-type p53 and p38 MAPK as well as decreasing p16 protein levels in human breast tissues. [PMID 16897432]
• p16 genes and their 9p21 locus have various roles in the pathogenesis of oral squamous cell carcinoma [PMID 19101490]
• There is a high level of association between the absence of p16 protein expression levels, CDKN2A gene promoter hypermethylation, and chromosome 9 aneuploidy. [PMID 17981214]
• review attempts to elucidate when and why p16(Ink4a) overexpression occurs, and to suggest possible implications of p16(Ink4a) in the diagnosis, prognosis and treatment of cancer [PMID 21297668]
• Over-expressed in squamous cell carcinoma of the mouth. [PMID 12738984]
• Hepatocellular carcinoma tissue p16INK4a promoter hypermethylation was significantly higher in male than that in female gender patients in frequency and was significantly increased in patients older than 50 years of age in intensity. [PMID 22192146]
• Premature senescence of balding dermal pipilla cells in vitro in association with expression of p16(INK4a)/pRB suggests that balding cells are sensitive to environmental stress [PMID 17989730]
• Report high-risk human papillomavirus infection and p16INK4a protein expression in benign/malignant laryngeal lesions. [PMID 18440161]
• A p14ARF splice germline mutation was detected for the first time in an Italian family with amelanotic melanoma. [PMID 19339902]
• Using a panel of four genes (AHRR, p16INK4a, MT1G, and CLDN3) resulted in sensitivity and specificity of 50% and 68%, respectively and may have utility for early detection of esophageal squamous dysplasia and early ESCC. [PMID 19137073]
• The detected opposite effects of p16(INK4a) at the levels of growth-regulatory galectins-1 and -3 shift the status markedly towards the galectin-1-dependent pro-anoikis activity. [PMID 20695889]
• Reconstituted Complex [PMID 10580009]
• the inactivation of CDKN2A by methylation occurs by distinct pathways according to the histological subtype and tumor location and depends on the Helicobacter pylori genotype [PMID 21849808]
• Promoter methylation of CDKN2A gene and lack of p16 expression characterize patients with hepatocellular carcinoma. [PMID 20569442]
• This study aims to further characterize p16 expression in trophoblastic lesions and squamous lesions of the upper female genital tract [PMID 20881863]
• aberrant methylation of p16(INK4a) is seen in in chromate workers with lung cancer [PMID 16828922]
• data indicate that EBNA3C and EBNA3A joint repression of CDKN2A p16(INK4A) and p14(ARF) is essential for lymphoblast cell line growth [PMID 21245331]
• Deletion of chromosome 9p21.3 is found in a many primary cutaneous diffuse large B-cell lymphoma, leg type patients and inactivation of the CDKN2A gene is associated with an unfavorable prognosis. [PMID 19020554]
• Studies identified significant association between variants in CDKN2A/B, CDKAL1 and TCF7L2, and type 2 diabetes in a Han Chinese cohort, indicating these genes as strong candidates conferring susceptibility to type 2 diabetes across different ethnicities. [PMID 20161779]
• PKCalpha is specifically required for TPA-induced ERK(MAPK) signaling to trigger gene expressions of p15(INK4b) and p16(INK4a) leading to HepG2 growth inhibition [PMID 15917995]
• Observational study of gene-disease association, gene-gene interaction, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator) [PMID 20879858]
• aberrant methylation of p16 and EDNRB was highly prevalent in leukemia patients in Taiwan. [PMID 18551992]
• p14ARF silencing may be an important mechanism in MCC tumorigenesis, and thus a potential target for therapeutic intervention in this highly aggressive tumor type. [PMID 18219279]
• p16INK4A hypermethylation is the principal mechanism of p16 protein underexpression and plays an important role in esophageal squamous cell carcinoma development. [PMID 20388212]
• high frequency of NRAS codon 61 mutations detected in primary hereditary melanomas may be the result of a hypermutability phenotype associated with a hereditary predisposition for melanoma development in patients with germline CDKN2A mutations [PMID 12783933]
• As2O3 up-regulates the expression of p16 and reverses its hypermethylation in the lymphoma cell line CA46. [PMID 20416177]
• CDKN2A (p16) promoter methylation or loss of expression in colorectal cancer is not independently associated with patient prognosis [PMID 20473920]
• These data question previously reported data supporting the prognostic relevance of both p16 and p27 proteins in early prostate cancer. [PMID 22221586]
• protein interaction mapping with Hdm2 [PMID 11718560]
• We found a pattern of global hypomethylation and promoter region hypomethylation of TP53 and p16 in cases of gastric cancer versus controls for a population of Omani Arabs. [PMID 22126203]
• tumor protein p53 mutations and p16(INK4A) promoter methylation, but not alterations in the H-Ras and K-Ras genes, might be involved in the malignant progression of pleomorphic adenomas into carcinoma [PMID 16447252]
• p16INK4 methylation causes gene silencing in primary colorectal carcinomas [PMID 12963980]
• CDK inhibitor p16 tumor suppressors were genes activated in early endometrial endometrioid carcinoma (stages I-II). [PMID 20015385]
• deregulation of the p16(INK4a) senescence pathway is involved in the development of myoepithelial tumours [PMID 19076682]
• p14ARF contributes to the p53 DNA damage response following ionizing irradiation. [PMID 15195142]
• High p53 expression level with low MDM2 and p14 ARF levels may be the characteristic features of low differentiated endometrial carcinoma. [PMID 18199985]
• In the ovarian cancer cell lines studied, cell growth was inhibited after transfection with p16(INK4a), p21(WAF1/Cip-1), and p53. [PMID 11733969]
• frequent p14 gene abnormalities (90%) and inactivation (40-60%) was in striking contrast to the same pathological subtype of systemic lymphoma, suggesting a difference in carcinogenesis between PCNSL and systemic lymphoma. [PMID 15649253]
• beta-catenin/TCF4 regulates cell cycle promoting (c-MYC, CYCLIN D(1)) and inhibiting genes (p16(INK4A)) at the same time in the mesenchymally differentiated tumor cells at the front of invasion. [PMID 18951899]
• Underexpression of p16 is associated with lymph node metastases in laryngeal squamous cell carcinoma. [PMID 18787961]
• Promoter methylation of p16INK4a is associated with biliary disease [PMID 12738733]
• INK4a and ARF may be repressed by Bmi-1 protein in a pathway leading to human colorectal carcinogenesis [PMID 14732230]
• Squamous cell tongue carcinoma patients with positive p16 surgical margins had 6.3%increased risk of having local recurrence. [PMID 19431196]
• Hypermethylation changes in exon 1 and exon 2 of p16 gene. Homozygous deletion frequency of exon 1 and exon 2 of p16 gene was 20 % and 10 %, respectively. No mutation found in exon 1 of p16 gene. Abnormal single strands found in 2 cases in exon 2. [PMID 12632489]
• Data show that deletion of CDKN2A and CDKN2B as well as the sequences just upstream and downstream were confirmed in SCC. [PMID 21757289]
• Sox5 can suppress platelet-derived growth factor B-induced glioma development in Ink4a-deficient mice through induction of acute cellular senescence. [PMID 19219070]
• CDKN2A is frequently homozygously deleted in bone fibrosarcoma patients, while other proteins are amplified. [PMID 19862822]
• this is the first report that experimentally links the tumour suppressor p16 to the process of lymphangiogenesis. [PMID 18577984]
• Results show that 18 of the 20 CDKN2A variants can be classed as loss of function mutations, whereas the results for two remain ambiguous. [PMID 19260062]
• INK4A was expressed in cervical intraepithelial neoplasms, but not in the normal uterine cervix. [PMID 16313047]
• Inactivation of p16/CDKN2 and p15/MTS2 is associated with prognosis and response to chemotherapy in ovarian cancer. [PMID 11992549]
• Results identified CDKN2A EX2 loci showing significant differential DNA methylation levels between tumor and non-tumor lung and highly significant hypermethylation in adenocarcinoma. [PMID 17967182]
• demonstrate genetically the oncogenic cooperation between defects on INK4a/ARF and p27, which are common alterations in human cancer [PMID 15378017]
• Genomic alterations by fine-mapping MLPA were validated at the DNA level for CDKN2A in head and neck squamous cell carcinoma; exon 1-alpha(p16INK4a) was identified as the smallest region of loss. [PMID 16618910]
• expression leading to endothelial cell proliferation is suppressed by Rem2 [PMID 18056257]
• CDKN2A promoter methylation is common in ovarian cancer. Quantification of CDKN2A methylation may be useful in distinguishing malignant from benign ovarian tumors or healthy ovarian tissue. [PMID 21728901]
• The results show that p16INK4A inhibits the acquisition of the adipose tissue macrophage-like phenotype. The age-related increase in p16INK4A level may thus contribute to type 2 diabetes risk. [PMID 21968977]
• Affinity Capture-MS; Affinity Capture-Western; Protein-peptide; Reconstituted Complex; Two-hybrid [PMID 22120712]
• p16(INK4A) gene silencing occurs prior to de novo methylation and histone remodelling. [PMID 19477956]
• Genome-wide association study of gene-disease association. (HuGE Navigator) [PMID 18489844]
• p16 and its methylation seems to play role in neuroblastoma tumorigenesis [PMID 19466588]
• Despite the fact that p16 is important in non-small cell lung cancer carcinogenesis, the data obtained do not allow the prognostic impact of this biological marker to be established. [PMID 18243403]
• Data show that mesenchymal stromal cells from umbilical cord blood do express p16(ink4a) protein. [PMID 19773264]
• These results indicate that MGMT and/or p16 aberrant methylation may play an important role in colorectal cancer. [PMID 18830187]
• specific modes of inactivation of p16 in Head and neck squamous cell carcinoma are related to specific patient risk profiles [PMID 18261630]
• The detection of the homozygous deletion of the p16 gene in pleural effusion may be a useful adjunct to the cytological and histological examinations of pleural effusion. [PMID 17675763]
• Three CDKN2A mutations (3/20; 15%), including one novel nonsense mutation (Trp110Stop) and two Arg24Pro missense alterations were found. [PMID 16374456]
• a significant minority of pancreatic intraepithelial lesions arising in patients with chronic pancreatitis show loss of p16 expression [PMID 14657708]
• all the childhood melanoma cases were associated with loss of p16 without any correlation with their Breslow thickness whereas all the Spitz nevi and benign melanocytic nevi had strong positive nuclear and cytoplasmic expression of p16 staining [PMID 21550132]
• Results describe the significance of p16INK4A and p15INK5B transcription suppression with hypermethylation of their genes’ 5’CpG islands during human hepatocellular carcinogenesis. [PMID 15112341]
• The frequency of p16 methylation in gastric mucosa of indefinite dysplasia was similar to that of dysplasia in human gastric mucosa with Helicobacter pylori infection. [PMID 18560456]
• p16 protein was up-regulated in A549 cells treated with ATRA. [PMID 11758167]
• Overexpression of p14ARF and pl6INK4A was associated with follicular adenomas, follicular carcinomas and papillary carcinomas of thyroid [PMID 17117177]
• The p14ARF transcript is clearly important in disease predisposition in a subset of melanoma pedigrees. [PMID 15856016]
• Report p16 methylation analysis in induced sputum from patients with lung cancer and non malignant disease. [PMID 22134685]
• Genetic variation at the CDKN2A/CDKN2B locus predicts stroke in hypertensive patients. [PMID 19293724]
• evaluated the expression of the tumour suppressors p14, p16 and p53 in pre-malignant and malignant squamous skin tumours, and its relation with risk factors for skin carcinogenesis (HPV, immune status and sun exposure) [PMID 18681909]
• analysis of the coordinated immediate responses by p16INK4A and p53 pathways in UVB-irradiated human skin cells [PMID 18719612]
• Study verified a statistically significant association between HPV and p16INK4. [PMID 21618514]
• expression of p16(INK4A) and Ki67 was significantly lower in penile verrucous carcinoma than in usual type squamous cell carcinoma. [PMID 19465901]
• p16 is preferentially expressed in eiomyosarcoma with only rare leiomyoma showing positivity [PMID 18162776]
• penetrance of mutations causing melanoma modified by MC1R genotype [PMID 11500805]
• NCOR1 (N-CoR) interacts with p-p14(ARF) (p14(ARF) promoter). [PMID 15729358]
• NCOR2 (SMRT) interacts with p-p14(ARF) (p14(ARF) promoter). [PMID 15729358]
• Promoter hypermethylation of p16 was observed. [PMID 17523078]
• p16 can serve as a reliable immunohistochemical marker in distinguishing uterine leiomyosarcomas from leiomyomas and its benign variants [PMID 18156978]
• p16, p53 and Ki-67 expressions were all negative in normal cervical epitheliums, but all positive in cervical intraepithelial neoplasia. [PMID 17545048]
• Methylation inactivation of P16 is associated with oral cancer [PMID 12684640]
• Lsh overexpression delays cell senescence by silencing p16(INK4a) in human fibroblasts. [PMID 19561196]
• The staining pattern for p16 in desmoplastic melanomas and Spitz nevi in conjunction with the histopathologic features, S100 staining, Ki67 proliferation index and clinical scenario may aid in the difficult differential diagnosis [PMID 19519606]
• role of p14ARF in breast cancer cell sensitivity to cisplatin [PMID 12200117]
• Genetic status of cell cycle regulators in squamous cell carcinoma of the oesophagus: the CDKN2A (p16(INK4a) and p14(ARF) ) and p53 genes are major targets for inactivation [PMID 11960918]
• hypermethylation of p16(INK4A) promoter is one of the epigenetic factors affecting the progress of sporadic breast carcinogenesis in Iranian patients. [PMID 19125298]
• immunohistochemical overexpression of p16 is linked to the presence and pathologic grade of human papillomavirus-induced precancerous cervical lesions. [PMID 17596760]
• Ectopic expression of RUVBL2 decreases the levels of ARF, whereas knockdown of RUVBL2 results in a marked increase in ARF levels. In addition, RUVBL2 down-regulates the levels of p53 in an ARF-dependent manner. [PMID 22285491]
• analysis of basaloid lesions of oral squamous epithelial cells and their association with HPV infection and P16 expression [PMID 20592349]
• There is a novel CDKN2A mutation detected in Spanish melanoma pedigree. [PMID 20653773]
• high expression of p16(INK4a) and low expression of Bmi1 are associated with endothelial cellular senescence in human cornea. [PMID 22509111]
• Decrease of expression of p16INK4 was significantly correlated with methylation. [PMID 17276933]
• p16 might act as a tumor suppressor in gastric carcinomas and appears to be more frequently methylated in lymphatic-invasive gastric carcinomas. [PMID 20683001]
• The overexpression of cdc2 was correlated with an infiltrative tumor border pattern. [PMID 21488187]
• Epithelial cells with methylation of p16 promoter sequences occur in focal patches of histologically normal mammary tissue of a substantial fraction of healthy, cancer-free women. [PMID 12670910]
• Promoter hypermethylation of RASSF1A, p16, and DAPK genes was detected in lung cancer. [PMID 20360646]
• Induction of p14(ARF) increased resistance to the folate antagonists. Depletion of thymidine in the medium reversed this resistance, indicating that p14(ARF) induction increases the reliance of these cells on thymidine salvage. [PMID 15205349]
• observations suggest that p14ARF tumor suppressor activity may be linked to its oligomerization status and sensitive to the redox status of the cell [PMID 12582152]
• p14ARF interacts with an unspecified isoform of Mdm2. [PMID 12582152]
• balance between Polycomb group (PcG) silencing and SWI/SNF activation affects epigenetic control of the INK4b-ARF-INK4a locus in malignant rhabdoid tumors [PMID 18332116]
• Homozygous deletion of ink4A is associated with poor survival in primary central nervous system lymphoma patients [PMID 11804283]
• p53 is functional in the absence of p14(ARF) in malignant pleural mesothelioma [PMID 16867217]
• ANRIL (INK4 locus) expression is associated with atherosclerosis risk at chromosome 9p21. [PMID 20056914]
• Improved survival in p16-positive oropharyngeal cancer patients seems to be due to lower rates of locoregional failure and deaths without failure. [PMID 20697079]
• Our results show that mutations of CDKN2A occur infrequently in these high-risk groups, and that they occur mainly in exons 1alpha and 2. [PMID 17218939]
• p53 and p16(INK4A) are promising candidates for the pulmonary molecular screening of heavy smokers healthy individuals. [PMID 18347195]
• Expression levels of MIF, VEGF and p16 were significantly higher in the carcinomas than those in cervical intraepithelial neoplasia or normal tissues. [PMID 19062717]
• smoking can influence the methylation level of the promoter region of p16(INK4a), and that this occurs in tumor tissues more frequently than in normal tissues [PMID 17923752]
• Did not find high mutation rates of CDKN2A in multiple primary and familial malignant melanoma in German patients. [PMID 17890059]
• mutations in melanoma [PMID 12072536]
• A hitherto unknown P14ARF/HDM2/SP1/TIMP3 signaling axis regulates TIMP3 expression via a balance between P14ARF & HDM2, independent of P53. P14ARF enhances SP1 transcriptional activity on TIMP3 by antagonizing inhibitory interaction of HDM2 with SP1. [PMID 22378045]
• p16-Rb pathway plans important role in tumor progression and prognosis in vertical growth phase melanomas [PMID 15547691]
• inactivation of p16INK4a/retinoblastoma pathway results in cell division in hepatocellular carcinoma through overexpression of Id-1 [PMID 12949053]
• p16 is a more sensitive and specific marker for identifying high-grade squamous intraepitelial lesions (HSIL-s). [PMID 17512033]
• EBV-positive gastric carcinomas revealed significantly more often gene hypermethylation of p16, p14 and APC. [PMID 20978327]
• Mutations in exon 1 and exon 2 of CDKN2A gene in a large group of 390 laryngeal cancers, were investigated. [PMID 19690981]
• only one germline CDKN2A mutation with functional significance, which was an exon 1 missense mutation resulting in a proline-to-leucine substitution in codon 48 [PMID 15305154]
• We found that p16(23Asp) was less efficient than p16(wt) in CDK4 binding, in inhibiting pRb phosphorylation, in inducing G1 cell cycle arrest; moreover, its pattern of distribution throughout the cell was suggestive of protein aggregation [PMID 19712690]
• Reduced or absent expression showed no significant correlation with the clinicopathological parameters of rhabdomyosarcoma, except for the age at diagnosis. [PMID 17243166]
• the p14ARF-p53-MDM2 pathway has a role in development of oral squamous cell carcinoma [PMID 16142358]
• v-Fos-stimulated invasion is independent of the pRb/p16(INK4a) and p53 tumor suppressor pathways and telomerase [PMID 14749371]
• p16-Leiden germline mutation may be involved in susceptibility to lung cancer and oral squamous cell carcinomas development in some patients [PMID 14985402]
• Aberrant p16 promoter methylation is associated with smokers and former smokers with nonsmall cell lung cancer [PMID 12918069]
• DeltaNp63alpha is preferentially sumoylated by SUMO2, instead of SUMO1, and p14(ARF) increases the efficiency of this process. [PMID 19829080]
• Alterations in both the p53 and p16-Rb pathways are associated with squamous cell carcinoma arising in mature cystic teratoma. [PMID 19067849]
• P16 hypermethylation induces the inactivation of p16 gene, plays an important role in hepatocarcinogenesis, and is associated with an increased risk of HCC and liver cirrhosis [review] [PMID 21799651]
• Suggest that several atherosclerosis-associated SNPs in the 9p21 locus affect the expression of ANRIL, which, in turn modulate cell growth, possibly via CDKN2A/B regulation. [PMID 22178423]
• No patient was found to be methylated for the promoter of TP73 while CDKN2A promoter was found to be methylated in 12/45 MM patients (26.6%) at diagnosis and in 1/4 WM patients [PMID 19423161]
• ATM and the ARF-p53 tumor suppressor pathway may cooperate in the pathogenesis of diffuse large B-cell lymphoma [PMID 12149228]
• a significant proportion of pancreatic ductal adenocarcinomas is characterized by simultaneous protein alterations regarding p16 & cyclin D1 genes; this mechanism of genetic deregulation in cell cycle potentially explains in part the aggressive phenotype [PMID 17600882]
• CDKN2A p.A148T is a melanoma susceptibility allele in Southern Brazil and is particularly common in patients with melanoma of predominantly European ancestry. [PMID 21895773]
• The functional analysis showed that this fragment like p16 can interact with CDK4/6, block the entry into S phase of the cell cycle and suppress growth as indicated by colony formation assay. [PMID 21053367]
• The first in vitro evidence for an important role of C DKN2A/p16 and CDK4 in chondrosarcoma cell survival and proliferation, is presented. [PMID 18624751]
• Authors developed and validated MelaPRO, an algorithm that provides germline CDKN2A mutation probabilities and melanoma risk to individuals from melanoma-prone families. [PMID 20068151]
• A trend towards increased lymph vascular space invasion was observed in p16 positive adenocarcinomas of the uterine cervix. There was no association between p16 expression and clinical stage, tumor grade, lymph node status and disease recurrence. [PMID 20405295]
• deletion of the locus harborning the p16 gene may be helpful for differentiating between malignant mesotheliomas and reactive mesothelial proliferations. [PMID 18327208]
• Examined association between MTHFR/thymidylate synthase gene polymorphisms and methylation of p16(INK4A) and hMLH1 genes in spontaneously aborted embryos with normal chromosomal integrity. [PMID 18177869]
• p14ARF acts through a common modification of diverse binding partners, including Ubc9 [PMID 15876874]
• This study suggests that simultaneous hypermethylation of both p16INK4a and p14ARF genes is greater prognostic value in sporadic human colorectal cancer. [PMID 16675157]
• the p16(INK4a)/pRb pathway mediates hSNF5-induced cellular senescence [PMID 14604992]
• Affinity Capture-Western [PMID 19085961]
• ULF is a bona fide E3 ligase for ARF and also suggest that ULF is an important target for activating the ARF-p53 axis in human acute myeloid leukaemia cells. [PMID 20699639]
• High frequency of hypermethylation of p16 was detected in the precancerous lesions; no hypermethylation was found in normal epithelium. Hypermethylation may be involved in the pathogenesis of oral precancerous lesions associated with betel-quid chewing. [PMID 18284544]
• Affinity Capture-Western; Reconstituted Complex [PMID 15210108]
• YY1 interacts with p14ARF. [PMID 15210108]
• These data suggest that the functional availability of Kaposi’s sarcoma-associated herpesvirus K-cyclin is largely dependent on the balance in expression between cellular CDK6 and p16INK4a. [PMID 20331971]
• of promoter hypermethylation of TIMP3, CDH1, DAPK, RASSF1A, p16INK4A and MGMT, only the epigenetic silencing of TIMP3 and CDH1 predicted a better outcome in head and neck squamous cell carcinoma [PMID 19148529]
• CDK4 and CDK6n delay senescence by kinase-dependent and p16INK4a-independent mechanisms. [PMID 17420273]
• Tumor suppressor and aging biomarker p16(INK4a) induces cellular senescence without the associated inflammatory secretory phenotype. [PMID 21880712]
• MC1R variants significantly increase penetrance of CDKN2A mutations in melanoma-prone families, especially with respect to multiple MC1R variants and to red hair color variants. [PMID 20189796]
• Meta-analysis of gene-disease association and gene-gene interaction. (HuGE Navigator) [PMID 20189796]
• p16 gene alterations are associated with papillary thyroid carcinoma [PMID 17195959]
• Analyzed promoter methylation of three candidate genes (p16, MGMT, and hMLH1) in 403 liquid-based cytology samples. [PMID 21747645]
• Differential expression of microenvironment genes and p16 locus deletion are associated with responses to radiation therapy and to first-line chemotherapy, respectively, in glioblastomas. [PMID 20822523]
• Co-crystal Structure [PMID 20655927]
• Loss (homozygous deletion or single copy) of CDKN2A was not prognostically significant in Ewing’s sarcoma. [PMID 17533400]
• Germline mutations in CDKN2A gene is not associated with suspected genetic predisposition to uveal melanoma. [PMID 20842456]
• high frequency of CDKN2A mutations are associated with multiple primary melanoma. [PMID 18983535]
• PAX3-FKHR fusion gene of rhabdomyosarcoma cooperates with loss of p16INK4A to promote bypass of cellular senescence [PMID 17638879]
• p53 contributes to a delayed form of senescence that requires telomere shortening, in p16-deficient melanocytes. These findings provide some basis for the role of p16 in melanoma susceptibility. [PMID 12759390]
• p16 expression is suppressed by miR-24 in human diploid fibroblasts and cervical carcinoma cells [PMID 18365017]
• p14(ARF) mRNA expression was notably increased in retinoblastoma but p14(ARF) protein was undetectable. [PMID 18644346]
• P16 inactivation by homozygous deletions or methylation is a frequent event in Japanese patients with malignant pleural mesothelioma [PMID 18395929]
• There was no difference in p16 or E6 transcripts between anal histologic grades [PMID 19567510]
• High p19(Arf)is associated with uterine leiomyomas. [PMID 20544840]
• Poor prognosis in liver fluke-related cholangiocarcinoma was associated with loss of p16(INK4a) expression. inactivation occurs through genetic events. [PMID 19200577]
• Overexpression of the p16 G101W mutant does not provoke the S-phase lengthening and the inhibition of Ser807/811-pRB and of Thr/Pro phosphorylation as wild-type p16(INK4a) does. (p16(INK4a)protein) [PMID 20703084]
• The expression of p16 in hypopharyngeal squamous cell carcinoma was significantly lower than that in normal epithelium. The positive rate of p16 was correlated with cervical lymph node metastases. [PMID 17634024]
• frequent inactivation of the p14ARF and p16INK4a genes may be an important mechanism for the dysfunction of p53 and Rb growth regulatory pathways during bladder cancer development. [PMID 12853838]
• Genetic alterations of INK4alpha/ARF locus and p53 are observed in human hepatocellular carcinoma. [PMID 12168936]
• EBV-LMP1, P53 and P16(INK4A) were overexpressed in 85.0%, 96.7% and 71.7% of Hodgkin lymphoma, respectively [PMID 21174181]
• Results indicate that TBX3 represses expression of p14(ARF) tumor suppressor in breast cancer. [PMID 18245468]
• p16 expression decrease is a significant event in endometrial carcinoma pathogenesis, and it is inversely correlated to tumor cell grade. [PMID 21797124]
• Sensor of morphological changes and of short-lived perturbations in cell cycle and in nucleolar function. [PMID 12360404]
• Overexpression of p16INK4a is induced by the human papillomavirus oncoprotein E7 and distinguishes dysplastic lesions from benign changes. [PMID 16350398]
• Increased expression of senescence-associated cell cycle inhibitor p16INK4a is associated with deteriorating renal transplants and diseased native kidney [PMID 15888044]
• aberrant CDKN2A promoter methylation is associated with preinvasive bronchial lesions in lung carcinoma [PMID 12115568]
• p16(INK4A) reconstitution in p16(INK4A)-deficient T-ALL cells induced cell cycle arrest in the presence of cyclin E and c-Myc expression, uncoupled growth from cell cycle progression and caused a sequential process of growth, differentiation and apoptosis [PMID 15800668]
• Data show that p16 is frequently expressed in squamous carcinoma of the cervix, vagina and vulva, but is not seen in cases of benign and low grade lesions. [PMID 15328914]
• It is suggested that upregulated CDKN2A with the concomitant downregulated cyclin gene family is partly involved in the small size of ACTH-secreting adenoma. [PMID 20616110]
• MYCL1, FHIT, SPARC, p16(INK4) and TP53 genes associated to lung cancer in idiopathic pulmonary fibrosis [PMID 12169206]
• the expression of p16INK4a correlated with advanced grade, triple negative tumors and mdm2 expression in invasive ductal breast carcinoma [PMID 20598349]
• CDKN2A FISH analysis can give false negative results in cases with small microdeletions [PMID 18160777]
• high telomerase activity with intact p16/Rb could be a marker of stem cell origin in cancer cells [PMID 20372796]
• Immunohistochemical p16ink4a expression is associated with HPV infection in high-grade squamous intraepithelial lesions and cervical cancer [PMID 19468254]
• P14ARF activates ERK, leads to its phosphorylation, and then stimulates the strong expression of p21, an inhibitor of cell cycle [PMID 21660463]
• 1. an increase in p16(ink4a) expression in normal lymphocytes is linked, in part, to the number of cell doublings before the occurrence of replicative senescence and (ii) this process is maintained in leukemic cell populations of numerous patients. [PMID 17475325]
• Role of the tumor suppressor ARF in oncogenesis [PMID 19514363]
• Loss of p16 expression was associated with hypermethylation of p16, MLH1 methylation and BRAF V600E mutation in Lynch syndrome. [PMID 19383812]
• c-Jun translocates B23 and ARF from the nucleolus after JNK activation by means of protein interactions [PMID 18316603]
• findings indicate that the inactivation of the CDKN2A/B locus is a frequent event in Ph+ acute lymphoblastic leukemia; deletions are frequently acquired at leukemia progression and are a poor prognostic marker [PMID 22134481]
• Effects of exogenous p16(ink4a) gene on biological behavior of human lung cancer cells are reported. [PMID 17393105]
• Observational study of gene-disease association. (HuGE Navigator) [PMID 20971364]
• CDKN2A was found to be methylated significantly more frequently in NSCLC tissues than in non-cancerous tissues. [PMID 18349282]
• CDKAL1 rs7754840 and rs7756992, but not CDKN2A/2B rs10811661, are associated with T2DM in Lebanese [PMID 22119613]
• Data show that the presence of p16(ink4a) accumulation and the absence of p53 overexpression are good surrogate markers for HPV-associated head and neck squamous cell carcinoma (HNSCC). [PMID 21607949]
• Large-scale analysis of cell cycle regulators in urothelial bladder cancer identifies p16 and p27 as potentially useful prognostic markers [PMID 18334837]
• TP53 mutation and CDKN2A methylation specifically interact to promote lung tumorigenesis in subjects with CYP1A1 risk genotype. [PMID 22154617]
• Polymorphisms in the p16 gene is associated with significantly poorer response to treatment in pancreatic cancer patients. [PMID 19020940]
• p14(ARF) nuclear overexpression in aggressive B-cell lymphomas is a sensor of malfunction of the common tumor suppressor pathways. [PMID 11830494]
• Affinity Capture-Western [PMID 18775696]
• p16INK4a reversibly inhibited cell growth. CDKIs mediate growth arrest in human osteosarcoma cell lines and provides further evidence of the existence of molecular links between cellular mortality and immortality. [PMID 11695244]
• Affinity Capture-Western [PMID 20395212]
• Affinity Capture-Western [PMID 20395212]
• the presence of CDKN2A mutations is associated with early onset, Multiple primary melanoma , Breslow thickness >0.4 mm and >/=3 affected family members in patients with cutaneous familial melanoma [PMID 21893440]
• The upregulation of ubap1 gene expression mainly and the downregulation of p16 gene expression mainly may simultaneously participate in the pathogenesis of acute leukemia. [PMID 21129243]
• Point mutations in CDKNA2 are uncommon event in the atypical nevi of persons with melanoma. [PMID 15724013]
• Multiple interacting domains contribute to p14ARF mediated inhibition of MDM2 [PMID 12085228]
• CDKN2A interacts with CDK4 [PMID 11556834]
• CDKN2A interacts with CDK6 [PMID 11556834]
• p16INK4a regulates keratinocyte clonal evolution and that inactivation of p16INK4a in epidermal stem cells is necessary for maintaining stemness. [PMID 16754749]
• patients with Gleason scale > 8 prostate cancer were characterized by the highest nuclear expression of p53, p16INK4a and Ki-67, and also by overexpression of cytoplasmic Bcl-2. [PMID 20010526]
• CDKN2A L94Q mutation may have a role in familial malignant melanoma [PMID 14646619]
• Together, a melanoma-predisposing gene (identified as CDKN2A in melanoma-prone families), number of nevi and/or dysplastic nevi, and sun-related covariates influence melanoma risk in both families unselected by family history and melanoma-prone families. [PMID 15150307]
• p16INK4a gene silencing during CIN was not determined to be a particularly rare event; however, it does not correlate with either HPV status or CIN grading. [PMID 16778587]
• HPV/p16-expression significantly improved outcome after radiotherapy in HNSCC [PMID 19910068]
• CDKN2A mutation carriers in the general population have a much lower risk of melanoma than that suggested by estimates obtained from multiple-case families. Familial clustering of melanoma occurs without identifiable mutations in CDKN2A. [PMID 16234564]
• The evaluation of a large number of actinic keratoses specimens have found a low gene mutation rate in low-graded AK lesions. p53 mutations rather than p16(INK4a) and/or Ha-ras mutations may be an early event in the development of AK to cutaneous SCC. [PMID 17488404]
• Contribution of large rearrangements in CDKN2A to the disease in melanoma-prone families was examined using multiplex ligation-dependent probe amplification. [PMID 18612309]
• Studies indicate that ARF is induced in response to DNA damage and inhibits, by direct interaction, the E3 ubiquitin ligase Mule. [PMID 21726556]
• results support a model in which the nucleolus serves as a p53 upstream sensor of cellular stress, and add to a growing body of evidence that nucleolar sequestration of ARF prevents activation of p53 [PMID 16627991]
• propose that the contrasting behavior of the two very similar INK4 proteins could reflect their respective roles in senescence versus differentiation [PMID 22080569]
• germline mutations of CDKN2A at risk for melanoma occur in the Brazilian population, and that these mutations likely originated in Europe [PMID 17713569]
• p16(INK4a) alteration has an important role in progression of gastrointestinal stromal tumors of the stomach. [PMID 21496871]
• The purpose of this study is to evaluate four different scoring methods of p16(INK4a) immunohistochemical staining in distinguishing between primary endocervical adenocarcinomas and endometrial adenocarcinomas [PMID 19347018]
• Loss of p16 due to hypermethylation of the promoter region is associated with non-small cell lung carcinomas. [PMID 21857254]
• This study demonstrates that ARF plays a direct role in regulation of Rb and suggests that inactivation of ARF may lead to defects in both p53 and Rb pathways in human cancer development. [PMID 17297463]
• Data suggest that P16(INK4A) may be a screening index in the HPV-associated carcinoma of gastric cardia. [PMID 21155014]
• Interference with Puma induction or expression of MCL1 or BCL2 significantly reduced both glucocorticoid- and FAS-induced cell death in p16INK4A-reconstituted leukemia cells. [PMID 19737931]
• Affinity Capture-MS; Affinity Capture-Western; Reconstituted Complex [PMID 15989956]
• ARF interacts with ARF-BP1. [PMID 15989956]
• the CDKN2A mutation status might be of prognostic value in metastatic cutaneous squamous cell carcinoma (CSCC). [PMID 19739123]
• Alterations of tumor suppressor genes such as CDKN2A and oncogenes such as ERBB2 play a role in the progression of intestinal metaplasia to adenocarcinoma in patients with Barrett’s esophagus. [PMID 21820152]
• Data show that the expression of CCND1/CDKN2A correlated with RB1 status in xenograft tumors in vivo. [PMID 21447152]
• Our findings provide no evidence that p16(INK4A)/p14(ARF) and p53 mutations contribute significantly to familial glioma. [PMID 20455025]
• p14(ARF) methylation was present in 61 of 188 colorectal cancers. 4 major haplotypes were identified within a block (-4256 T–>C, -3631 T–>C, -1477 G–>A, +20,188 T–>C). p14(ARF) promoter methylation was associated with CCAT and CTAC haplotype. [PMID 18327804]
• P16 can serve as an additional diagnostic marker for distinction of uterine serous carcinomas from endometrioid carcinomas. [PMID 19623034]
• In invasive urothelial carcinomas, the p16-pRb pathway, the p14(ARF)-p53 pathway, or both pathways were altered or not activated and were thus involved in invasive bladder tumorigenesis. [PMID 15257544]
• K-RAS point mutations, and anomalies of p16-RB1-cyclin D pathway could occur before LOH on 10q23 (PTEN) and microsatellite instability during tumor progression. [PMID 19140325]
• the gene CDKN2A, is subject to homozygous and heterozygous deletions in neuroblastoma tumors [PMID 18664255]
• Dietary intakes of folate, vitamins B2, B6, B12, and methionine were not associated with likelihood of promoter methylation of E- cadherin, p16, and RAR-beta2. [PMID 21916701]
• The binding between p16 and HIF-1a protein may alter HIF-1a’s ability to transactivate VEGF expression in breast tumor cells. [PMID 20307196]
• common genetic polymorphisms in DNA repair, apoptosis and immune response pathways may modify the risk of cutaneous malignant melanoma families with or without CDKN2A mutations. [PMID 19626699]
• In a mixed uveal and cutaneous melanoma family, CDKN2A is demonstrated for the first time to be a uveal melanoma (UM)susceptibility gene, loss of function of which is involved in the pathogenesis of UM. [PMID 14506702]
• Flavopiridol in low, clinically achievable concentrations may have significant cytostatic effects, particularly in p16- melanoma cells, and may provide new molecular-based therapies for melanoma, particularly when combined with anti-apoptotic agents. [PMID 12777976]
• p16((INK4a)) methylation results in transcriptional silencing and defines a group of colorectal cancers with a poor prognosis. [PMID 19779933]
• CDKN2A deletion is a significant secondary abnormality in childhood acute lymphoblastic leukemia strongly correlated with phenotype and genotype [PMID 18838613]
• tobacco smoking may be associated with an increased incidence of aberrant promoter methylation of the p16 and MGMT genes in non-small cell lung cancer [PMID 16533425]
• p34(SEI-1) and p16(INK4A) have different roles in development of squamous cell carcinoma of the head and neck [PMID 16201750]
• increased nucleolar expression of p14ARF and an absence of nucleolar or nucleoplasmic p14ARF/Hdm2 complexes in Reed Sternberg cells in Hodgkin’s lymphoma [PMID 11839577]
• Results suggest that p53 degradation and inhibition of p14(ARF) signaling are independent functions of HPV16 E6, and that long-term proliferation of mammary epithelial cells requires inactivation of the p14(ARF)-p53 pathway. [PMID 14966292]
• By comparing the expression of p53, cyclin D1, p16, hTERT, and TSP-1 in spontaneously regressing keratoacanthoma and squamous cell carcinoma, the changes in the expression of these proteins to specific stages of skin carcinogenesis, is defined. [PMID 17198740]
• induces G2 arrest and apoptosis independently of p53 leading to regression of tumours established in nude mice [PMID 12660818]
• Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator) [PMID 20876876]
• DDB1-CUL4 and MLL1 complexes constitute a novel pathway that mediates p16 activation during oncogenic checkpoint response. [PMID 19208841]
• DNA sequence analysis of the breakpoints and junctions of CDKN2A and CDKN2B gene deletions in diffuse large B-cell lymphomas [PMID 21638516]
• The abnormal methylation of p16(INK4a) gene may not play a significant role in the early stage of breast cancinogenesis, but may play a role of in progression. [PMID 21055153]
• p16/INK4a gene inactivation by hypermethylation is associated with aggressive variants of monoclonal gammopathies. [PMID 11920239]
• Differences in oncoprotein expression between endometriotic and adenomyotic tissues provide further evidence that the pathogenesis of endometriosis is different from that of adenomyosis. [PMID 16616093]
• Phenylhexyl isothiocyanate can reduce the methylation level of p16 gene in U266 cells. [PMID 18928595]
• p16(INK4a) was up-regulated at the invasive front of the majority of basal cell carcinomas with infiltrative growth patterns, followed by ceased proliferation. [PMID 12702553]
• evidence that p16(INK4a) is degraded by N-terminal ubiquitination in a cell density-dependent manner [PMID 15254040]
• the melanoma-predisposing proline-48-threonine mutation of p16 in Hungarians may show a common founder either in Italy or in Hungary [PMID 17625456]
• Knockdown of MOV10 in human fibroblasts leads to the upregulation of the INK4a. [PMID 20543829]
• Data show that 87.9% of the patients with invasive lesion showed overexpression of p16(INK4a), in comparison with 37.6% of those with in situ lesion, demonstrating overexpression of p16(INK4a) as a risk of invasion of the basal layer by dysplastic cells. [PMID 19100258]
• The N-terminal half of p16 is significantly more sensitive to proteolysis in both tumor-derived mutant proteins than in the wild type, suggesting that stabilization of the N-terminal region could be a useful strategy for future therapeutic development. [PMID 12009890]
• The induction of p16ink4a by growth factors was mediated through the mitogen-activated protein kinase (MAPK) cascade. [PMID 19582773]
• data reinforce the hypothesis that ARF is a melanoma susceptibility gene [PMID 15937071]
• Of the molecular modifications described for renal carcinoma, aberrations in the p16 gene are frequent [PMID 18452812]
• Data show that in the presence of a functional p53/Puma/Bax-signaling axis, p14(ARF)-triggered apoptosis is enhanced by loss of p21(CDKN1)-mediated cell cycle checkpoint control. [PMID 20419447]
• results show that germline mutations at the CDKN2A locus are rare in sporadic melanoma in Latvia [PMID 17505264]
• Aberrant expression may reflect early genetic events during the progression of Barrett esophagus-associated carcinogenesis. [PMID 18665038]
• knockdown of BMI-1 expression can induce cell-cycle arrest and up-regulate p16INK4a, HOXA9 and HOXC13 in HeLa cells [PMID 20661663]
• p16 might act as a tumor suppressor in colorectal carcinomas and was more frequently methylated in advanced colorectal carcinomas. [PMID 19331161]
• increases of p16(INK4a) and p21(WAF1/cip1) expression in response to BMP4 were mediated by the Smad1/5/8 signaling pathway. [PMID 19269967]
• promoter methylation studied in 80 patients with head and neck squamous cell carcinoma (HNSCC) [PMID 12082610]
• Exogenous P16 has negative effects on the malignant proliferation of the bladder cancer cells, and it may be considered as target for potential anticancer drugs. [PMID 16100943]
• Data show that although p16(INK4A) immunohistochemistry may be helpful in distinguishing oropharyngeal nonkeratinizing SCC from branchial cleft cysts in FNAB specimens, it is not helpful in cases of keratinizing SCC typically negative for p16(INK4A). [PMID 19365840]
• p16 is not a reliable indicator of high-risk human papillomavirus infection in squamous cell carcinomas of the lung, skin, and esophagus. [PMID 21840041]
• Our finding suggests that polymorphisms in DNA repair genes, POLN and PRKDC, were associated with increased melanoma risk in melanoma families with and without CDKN2A mutations. [PMID 21671477]
• TWIST plays a key role in the continuous proliferation of immortalized cells. Over-expression of TWIST results in down-regulation of p14(ARF), which leads to the impairment of DNA damage checkpoint in response to genotoxic stress. [PMID 17690110]
• A lesser proportion of the p16 deletion in T-ALL patients was observed. [PMID 18617057]
• Transgenic expression leads to enhanced apoptosis and differentiation arrest of immature thymocytes [PMID 11859122]
• The immunoexpression of p16INK4a was significantly increased in the HPV-positive group compared to the HPV-negative group. [PMID 21526487]
• expression of P16(INK4A) in developing TAL1xLMO1 thymocytes blocks leukemogenesis in the majority of the mice [PMID 17507663]
• Loss of heterozygosity of p16 correlates with minimal residual disease at the end of the induction therapy in non-high risk childhood B-cell precursor acute lymphoblastic leukemia. LOH of p16 may be a marker of chemotherapy resistance in BCP-ALL. [PMID 12127556]
• Study concludes that CDKN2A is a promising new candidate gene potentially contributing to AD susceptibility on chromosome 9p. [PMID 18761660]
• Data indicate that MYCN is a central modulator of the p53/MDM2/p14ARF negative feedback loop. [PMID 21725357]
• ARF attenuates c-Myc independently of the ARF-p53 axis [PMID 15199070]
• The potential use of p16 methylation status in predicting the outcome of multiple myeloma patients suggests the applicability of demethylating agents in treatment. [PMID 20721556]
• Hypermethylation of CDKN2A is associated with acute lymphoblastic leukemia of childhood. [PMID 19484265]
• Expression of a novel, circular ANRIL isoforms (cANRIL) is correlated with INK4/ARF transcription and atherosclerosis risk. [PMID 21151960]
• p16INK4a immunohistochemistry as an adjunct to conventional H&E-stained specimens contributes to a more reproducible diagnosis of cervical intraepithelial neoplasia and may be a valuable aid for the interpretation of cervical histology. [PMID 18223479]
• Investigated the methylation of the SFRP2, P16, DAPK1, HIC1, and MGMT genes, as well as the mutation of amino acid codons 12 and 13 of the KRAS gene in normal and tumor tissue DNA of patients diagnosed with sporadic colorectal cancer. [PMID 20682398]
• Observational study of gene-disease association, gene-gene interaction, and gene-environment interaction. (HuGE Navigator) [PMID 20889853]
• Aberrant BRAF and INK4A functionally interact to promote growth and survival of melanoma cells. [PMID 18402768]
• The expression of EGFR, Ki67, p16 in middle ear cholesteatoma was significantly higher compared with controls. [PMID 19157151]
• The data obtained suggest that p16 protein expression per se may not represent a marker of retinoblastoma protein (pRb) pathway disturbance in acral lentiginous melanoma tumorigenesis. [PMID 20415670]
• No association was found between p16 expression and host phenotype but loss of p16 staining was associated with thicker lesions and a high mitotic index. In the progression of sporadic primary melanomas, p16 loss may be associated with aggressive tumours. [PMID 12459643]
• p16 methylation occurred in every stage of leukoplakia cancerization and oral squamous cell carcinoma progression. [PMID 15842853]
• cells from patients with diabetic nephritis exhibit significantly lower protein and mRNA expression of p16. [PMID 12753296]
• E47 is involved in the regulation of p16(INK4a) transcription in cellular senescence [PMID 15138269]
• p14ARF interacts with TBP-1. [PMID 14665636]
• the CDKN2A A148T variant seems to contribute to early-onset breast cancer in Poland [PMID 17061045]
• Epigenetic repression of p16(INK4A) by latent Epstein-Barr virus requires the interaction of EBNA3A and EBNA3C with CtBP. [PMID 20548956]
• [over]expression provides evidence of the malignant potential in oral lichen planus [PMID 21426400]
• Observational study, meta-analysis, and genome-wide association study of gene-disease association. (HuGE Navigator) [PMID 19578367]
• This review focuses on the extensive studies that uncover the involvement of INK4 proteins in senescence, apoptosis, DNA repair, and multistep oncogenesis. [PMID 17654117]
• The p16INK4A promoter was heavily methylated in a subset of paragangliomas and showed moderate suppression in malignant cases [PMID 18509008]
• the RASSF1A but not p16INK4a methylated promoter region has a role in progression of non-small cell lung cancer [PMID 15447998]
• There is over-expression of E2F-1 gene and deletion of p14(ARF) gene in the tumorigenesis of the lung cancer in Gejiu and Xuanwei regions in Yunnan Province. [PMID 20039540]
• Expression of p16INK4 and also cyclin B1 correlate significantly with long-term survival in renal cell carcinoma. [PMID 17668170]
• overexpression of p16INK4a and p73 may be involved in breast cancer and associated with poor tumor characteristics [PMID 15450420]
• p16(INK4a) ELISA has a similar sensitivity and slightly better specificity for CIN3 [PMID 17294450]
• p53 and p16INK4a proteins and bcl-2 oncoprotein correlate with the proliferative index and tumor thickness in malignant skin melanoma [PMID 21108607]
• Single nucleotide polymorphisms in CDKN2A is associated with Philadelphia positive acute lymphoblastic leukemia. [PMID 21414664]
• comprehensive analysis of the deletion and the methylation profile of CDKN2A (hereafter identified separately as p16 and p14, for the different proteins encoded) and CDKN2B (hereafter p15) in 91 newly diagnosed B-ALL patients (61 children, 30 adults). [PMID 19837270]
• Studies indicate that the mutation patterns of TP53, ATM and CDKN2A support the oncogene-induced DNA replication stress model, which attributes genomic instability and TP53 and ATM mutations to oncogene-induced DNA damage. [PMID 20177397]
• Phenotypic characteristics were examined in melanoma-prone southern Swedish CDKN2A (p16-113insArg/p14ARF-128insSer) mutation families, in relation to the CDKN2A genotype, nevi, clinically atypical nevi (CAN) and melanoma [PMID 20526219]
• Immunocytologic analysis of p16(INK4a) expression in cytologic samples is a useful ancillary tool for detection of urothelial carcinoma with infiltrating potential. [PMID 19846821]
• p16 interacts with cdk6. This interaction was modeled on a demonstrated interaction between human p16 and cdk6 from an unspecified species. [PMID 9482104]
• p16 interacts with cdk4. This interaction was modeled on a demonstrated interaction between human p16 and cdk4 from an unspecified species. [PMID 9482104]
• Increase in p16(INK4a) methylation in serum is associated with recurrence of colorectal cancer. [PMID 21617221]
• Identification of a novel germline variant, G89D, that was strongly associated with increased melanoma risk and appeared to be an Icelandic founder mutation. [PMID 18178632]
• The consistency of p16 protein deletion in different stages of nasopharyngeal carcinoma (NPC) suggests that the deletion of p16 protein is an early event in the development of NPC. [PMID 12419160]
• Andrographolide inhibits human colorectal cancer Lovo cell growth by G1-S phase arrest and inducing the expression of p53, p21 and p16. [PMID 18619950]
• p16(INK4a) inactivation is not required to immortalize primary human mammary epithelial cells. [PMID 12420227]
• HSP70 as a critical regulator of ARF-mediated autophagy, and reinforce the importance of mitochondrial trafficking of ARF for its autophagy function [PMID 21738007]
• Shelterin dysfunction and ensuing upregulation of INK4a promote accelerated aging of HIV-1-specific T cells during progressive HIV-1 infection. [PMID 22398292]
• Inhibitor shows antitumor effect on glioma cells [PMID 12698196]
• expression in malignant melanomas with or without a contiguous nevus remnant [PMID 15305164]
• p14(ARF) polymorphisms may be susceptible markers of the risk of developing a second primary malignancy in patients with squamous cell carcinoma of the head and neck. [PMID 21381012]
• the G500 CDKN2A allele was associated with no defined telomere maintenance mechanism glioblastoma multiforme from older individuals with poorer survival [PMID 22046342]
• Results uncover an unexpected role for the p16(INK4a)-Rb pathway and provide a new insight into how senescent cell-cycle arrest is enforced. [PMID 17028578]
• The Aberrant expression of Cyclin-Dependent Kinase Inhibitor p16 were determined in bone marrow samples of children with de novo B-lineage (n=170) and T-lineage (n=25) acute lymphoblastic leukemia (ALL). [PMID 15878620]
• we have shown that common variation at 9p21.3 (rs3731217, intron 1 of CDKN2A) influences acute lymphoblastic leukemia risk (odds ratio = 0.71, P = 3.01 x 10(-11)), irrespective of cell lineage. [PMID 20453839]
• The combination of L1 and p16(INK4a) has a higher diagnostic accuracy than L1 or p16(INK4a) alone in diagnosis of cervical lesions. [PMID 19941368]
• ARF promoter is regulated by E2F through both direct binding to the promoter sequences and indirectly, probably by being tethered to the ARF promoter by Sp1-like factors. [PMID 11883935]
• An important role for autophagy in tumor suppression via full-length ARF in both p53-dependent and p53-independent manners, depending on cellular context. [PMID 18199527]
• Inactivation of p14ARF and p16INK4a genes by either homozygous deletion or promoter hypermethylation may be important for the molecular pathogenesis of salivary malignant tumors [PMID 12684623]
• Low CDKN2A is associated with lung cancer . [PMID 20565749]
• Demonstration of centrosome dysfunction in cells due to loss of p16(INK4a) suggests that, under the appropriate conditions, these cells can become aneuploid [PMID 16464125]
• Loss of p16 expression is associated with the stem cell characteristics of surface markers and therapeutic resistance in estrogen receptor-negative breast cancer. [PMID 21717460]
• a causal role of p16(INK4A) disruption in modulating DNA hypermethylation, and identify a dynamic and active process whereby epigenetic modulation of gene expression is activated as an early event in breast tumor progression [PMID 16766534]
• Examined regulatory mechanisms of p16 expression. Exogenously expressed Id1 suppressed up-regulation of p16 by Hepatocyte growth factor and the antiproliferative effect of HGF. Knockdown of Id1 sig. enhanced activity of the p16 promoter with ERK. [PMID 19567783]
• Frequencies of LOH in two microsatellite sites, D9s171 and D9s1604, in p16 genome were associated with development of gastric cancer. No correlation between LOH frequency and cell differentiated types of tumor cells or clinical stages. [PMID 12632492]
• CDKN2a polymorphism 500 C/G correlated with Ala148Thr but) no correlation was observed between the 500 C/G polymorphism and age, localization of the primary melanoma and survival time. [PMID 17351674]
• HBP1 targets P16(INK4A), upregulating its expression and consequently is involved in Ras-induced premature senescence. [PMID 20581871]
• Immunohistochemical tests for p16 (INK4A) and cyclin E could help in early diagnosis of cervical carcinoma. [PMID 18301453]
• P16INK4A protein plays a significant role in the formation of benign neoplasms and their malignant counterparts derived from follicular thyroid cell. [PMID 15757201]
• The variable expression levels of cell-cycle inhibitor genes CDKN2A, CDKN2B, and CDKN1B due to regulatory polymorphisms could indeed influence the risk of childhood pre-B ALL and contribute to carcinogenesis. [PMID 17008550]
• mutant p53 loses its ability to suppress DNMT1 expression, and thus enhances methylation levels of the p16 ( ink4A ) promoter and subsequently down-regulates p16(ink4A )protein. [PMID 18038118]
• There is a significant statistical difference between immunohistochemical expression of p16(INK4a) and Ki-67 in HPV-associated dysplastic and non-dysplastic vulvar lesions. [PMID 20198771]
• The percentage of families with two melanoma cases/family harboring a mutation was low (7%, 2/27), but rose to 45% (9/20) if one of the melanoma patients carried multiple melanomas or if pancreatic cancer was present in that family. [PMID 11807902]
• Methylation of the p16 gene CpG island ia common to all three histological patterns associated with Cushing’s disease. [PMID 15014032]
• p16INK4a promoter mutations are frequent in primary sclerosing cholangitis (PSC) and PSC-associated cholangiocarcinoma. [PMID 12360471]
• Induction of senescence by BRAF may explain the low-grade pathobiology of pilocytic astrocytoma, whereas worse clinical outcomes in tumors lacking p16INK4a expression reflect failure to induce senescence or an escape from oncogene-induced senescence. [PMID 21636552]
• p16INK4A is phosphorylated upon Cdk4 association [PMID 12529334]
• Results substantiate the critical role of CTCF in establishing and maintaining p16INK4A and other tumor suppressor genes in higher-order chromosomal domains through appropriate boundary formation. [PMID 19450526]
• No significant differences between ocular melanoma cases and controls in the frequency of any of the four most common variants of CDKN2A, and no melanoma case carried a deleterious germline CDKN2A mutation. [PMID 12883368]

PubMed Articles

Recent articles:

• Lessard F et al. “The cellular abundance of the essential transcription termination factor TTF-I regulates ribosome biogenesis and is determined by MDM2 ubiquitinylation.” Nucleic Acids Res. 2012 Jul 1;40(12):5357-67. PMID 22383580
• Dai MS et al. “Physical and functional interaction between ribosomal protein L11 and the tumor suppressor ARF.” J Biol Chem. 2012 May 18;287(21):17120-9. PMID 22467867
• Su C et al. “PIWIL4 regulates cervical cancer cell line growth and is involved in down-regulating the expression of p14ARF and p53.” FEBS Lett. 2012 May 7;586(9):1356-62. PMID 22483988
• Lichterfeld M et al. “Shelterin dysfunction and p16(INK4a)-mediated growth inhibition in HIV-1-specific CD8 T cells.” J Virol. 2012 May;86(10):5533-40. PMID 22398292
• Wang Y et al. “High expression of p16INK4a and low expression of Bmi1 are associated with endothelial cellular senescence in the human cornea.” Mol Vis. 2012;18:803-15. PMID 22509111
• Zerrouqi A et al. “P14ARF inhibits human glioblastoma-induced angiogenesis by upregulating the expression of TIMP3.” J Clin Invest. 2012 Apr 2;122(4):1283-95. PMID 22378045
• Aidé S et al. “Promoter hypermethylation of death-associated protein kinase and p16 genes in vulvar lichen sclerosus.” J Low Genit Tract Dis. 2012 Apr;16(2):133-9. PMID 22371043
• Dragomir LP et al. “P53, p16 and Ki67 immunoexpression in oral squamous carcinomas.” Rom J Morphol Embryol. 2012;53(1):89-93. PMID 22395505
• Zhang X et al. “The tRNA methyltransferase NSun2 stabilizes p16INK⁴ mRNA by methylating the 3’-untranslated region of p16.” Nat Commun. 2012 Mar 6;3:712. PMID 22395603
• Ghiorzo P et al. “CDKN2A is the main susceptibility gene in Italian pancreatic cancer families.” J Med Genet. 2012 Mar;49(3):164-70. PMID 22368299

Top Pubmed articles linked to gene CDKN2A matching any search term:

• Fagerholm E et al. “SNP in the genome-wide association study hotspot on chromosome 9p21 confers susceptibility to diabetic nephropathy in type 1 diabetes.” Diabetologia. 2012 Sep;55(9):2386-2393. PMID 22643932
• Tang DQ et al. “In vitro generation of functional insulin-producing cells from human bone marrow-derived stem cells, but long-term culture running risk of malignant transformation.” Am J Stem Cells. 2012 Jun 30;1(2):114-127. PMID 22833839
• Agrawal KL et al. “A seldom case of primary urethral malignant melanoma and breast cancer detected by (18)F-FDG PET/CT.” Hell J Nucl Med. 2012 May-Aug;15(2):157-8. PMID 22741154
• Kang R et al. “AGER/RAGE-mediated autophagy promotes pancreatic tumorigenesis and bioenergetics through the IL6-pSTAT3 pathway.” Autophagy. 2012 Jun 1;8(6). PMID 22722139
• Li H et al. “Association between type 2 diabetes and rs10811661 polymorphism upstream of CDKN2A/B: a meta-analysis.” Acta Diabetol. 2012 May 24;. PMID 22623142
• Braun TR et al. “A replication study of GWAS-derived lipid genes in Asian Indians: the chromosomal region 11q23.3 harbors loci contributing to triglycerides.” PLoS One. 2012;7(5):e37056. PMID 22623978
• Fukuda A et al. “Bmi1 Is Required for Regeneration of the Exocrine Pancreas in Mice.” Gastroenterology. 2012 May 17;. PMID 22609312
• Ekelund M et al. “Genetic prediction of postpartum diabetes in women with gestational diabetes mellitus.” Diabetes Res Clin Pract. 2012 May 14;. PMID 22591707
• Kurzawski M et al. “Analysis of common type 2 diabetes mellitus genetic risk factors in new-onset diabetes after transplantation in kidney transplant patients medicated with tacrolimus.” Eur J Clin Pharmacol. 2012 May 9;. PMID 22569928
• Winkler C et al. “Lack of association of type 2 diabetes susceptibility genotypes and body weight on the development of islet autoimmunity and type 1 diabetes.” PLoS One. 2012;7(4):e35410. PMID 22558147
• Hribal ML et al. “Glucose tolerance, insulin sensitivity and insulin release in European non-diabetic carriers of a polymorphism upstream of CDKN2A and CDKN2B.” Diabetologia. 2011 Apr;54(4):795-802. PMID 21234743
• Voight BF et al. “Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis.” Nat Genet. 2010 Jul;42(7):579-89. PMID 20581827
• Li Y et al. “Glucose restriction can extend normal cell lifespan and impair precancerous cell growth through epigenetic control of hTERT and p16 expression.” FASEB J. 2010 May;24(5):1442-53. PMID 20019239
• Kang ES et al. “Association of common type 2 diabetes risk gene variants and posttransplantation diabetes mellitus in renal allograft recipients in Korea.” Transplantation. 2009 Sep 15;88(5):693-8. PMID 19741467
• Lin X et al. “Risk prediction of prevalent diabetes in a Swiss population using a weighted genetic score–the CoLaus Study.” Diabetologia. 2009 Apr;52(4):600-8. PMID 19139842
• Cho YM et al. “Type 2 diabetes-associated genetic variants discovered in the recent genome-wide association studies are related to gestational diabetes mellitus in the Korean population.” Diabetologia. 2009 Feb;52(2):253-61. PMID 19002430
• Tabara Y et al. “Replication study of candidate genes associated with type 2 diabetes based on genome-wide screening.” Diabetes. 2009 Feb;58(2):493-8. PMID 19033397
• van Hoek M et al. “Predicting type 2 diabetes based on polymorphisms from genome-wide association studies: a population-based study.” Diabetes. 2008 Nov;57(11):3122-8. PMID 18694974
• Matarin M et al. “Whole genome analyses suggest ischemic stroke and heart disease share an association with polymorphisms on chromosome 9p21.” Stroke. 2008 May;39(5):1586-9. PMID 18340101
• McPherson R et al. “A common allele on chromosome 9 associated with coronary heart disease.” Science. 2007 Jun 8;316(5830):1488-91. PMID 17478681