Gene Symbol: p16
Description: cyclin dependent kinase inhibitor 2A
Alias: ARF, CDK4I, CDKN2, CMM2, INK4, INK4A, MLM, MTS-1, MTS1, P14, P14ARF, P16, P16-INK4A, P16INK4, P16INK4A, P19, P19ARF, TP16, cyclin-dependent kinase inhibitor 2A, CDK4 inhibitor p16-INK4, alternative reading frame, cell cycle negative regulator beta, cyclin-dependent kinase 4 inhibitor A, cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4), multiple tumor suppressor 1
Species: human
Products:     p16

Top Publications

  1. Jung A, Briolat J, Millon R, de Reyniès A, Rickman D, Thomas E, et al. Biological and clinical relevance of transcriptionally active human papillomavirus (HPV) infection in oropharynx squamous cell carcinoma. Int J Cancer. 2010;126:1882-1894 pubmed publisher
  2. Demenais F, Mohamdi H, Chaudru V, Goldstein A, Newton Bishop J, Bishop D, et al. Association of MC1R variants and host phenotypes with melanoma risk in CDKN2A mutation carriers: a GenoMEL study. J Natl Cancer Inst. 2010;102:1568-83 pubmed publisher
    ..Results show that MC1R variants, hair color, and number of nevi were jointly associated with melanoma risk in CDKN2A mutation carriers. This joint association may have important consequences for risk assessments in familial settings. ..
  3. Zhao N, Ang M, Yin X, Patel M, Fritchie K, Thorne L, et al. Different cellular p16(INK4a) localisation may signal different survival outcomes in head and neck cancer. Br J Cancer. 2012;107:482-90 pubmed publisher
    ..human papilloma infection, including direct assessment of the virus as well as an associated tumour suppressor gene p16, are considered reproducible...
  4. Yang X, Pfeiffer R, Wheeler W, Yeager M, Chanock S, Tucker M, et al. Identification of modifier genes for cutaneous malignant melanoma in melanoma-prone families with and without CDKN2A mutations. Int J Cancer. 2009;125:2912-7 pubmed publisher
    ..Our findings support the hypothesis that common genetic polymorphisms in DNA repair, apoptosis and immune response pathways may modify the risk of CMM in CMM-prone families with or without CDKN2A mutations. ..
  5. Freathy R, Bennett A, Ring S, Shields B, Groves C, Timpson N, et al. Type 2 diabetes risk alleles are associated with reduced size at birth. Diabetes. 2009;58:1428-33 pubmed publisher
    ..Our results are in keeping with the fetal insulin hypothesis and provide robust evidence that common disease-associated variants can alter size at birth directly through the fetal genotype. ..
  6. Yang X, Liang X, Pfeiffer R, Wheeler W, Maeder D, Burdette L, et al. Associations of 9p21 variants with cutaneous malignant melanoma, nevi, and pigmentation phenotypes in melanoma-prone families with and without CDKN2A mutations. Fam Cancer. 2010;9:625-33 pubmed publisher
    ..These genetic variants may, at least partially, exert their effects through nevi and tanning ability. ..
  7. Vivo M, Ranieri M, Sansone F, Santoriello C, Calogero R, Calabrò V, et al. Mimicking p14ARF phosphorylation influences its ability to restrain cell proliferation. PLoS ONE. 2013;8:e53631 pubmed publisher
    ..Here, we show for the first time that p14ARF is a PKC target...
  8. Bishop D, Demenais F, Iles M, Harland M, Taylor J, Corda E, et al. Genome-wide association study identifies three loci associated with melanoma risk. Nat Genet. 2009;41:920-5 pubmed publisher
    ..Despite wide variation in allele frequency, these genetic variants show notable homogeneity of effect across populations of European ancestry living at different latitudes and show independent association to disease risk. ..
  9. Kordi Tamandani D, Moazeni Roodi A, Rigi Ladez M, Hashemi M, Birjandian E, Torkamanzehi A. Analysis of methylation patterns and expression profiles of p14ARF gene in patients with oral squamous cell carcinoma. Int J Biol Markers. 2010;25:99-103 pubmed
    To analyze the promoter methylation profile and mRNA expression of the p14ARF gene in oral squamous cell carcinoma (OSCC).

More Information

Publications350 found, 100 shown here

  1. Haferkamp S, Becker T, Scurr L, Kefford R, Rizos H. p16INK4a-induced senescence is disabled by melanoma-associated mutations. Aging Cell. 2008;7:733-45 pubmed
    The p16(INK4a)-Rb tumour suppressor pathway is required for the initiation and maintenance of cellular senescence, a state of permanent growth arrest that acts as a natural barrier against cancer progression...
  2. Hwang H, Tse C, Rodriguez S, Gown A, Churg A. p16 FISH deletion in surface epithelial mesothelial proliferations is predictive of underlying invasive mesothelioma. Am J Surg Pathol. 2014;38:681-8 pubmed publisher
    ..Homozygous deletion of p16 (CDKN2A) by fluorescence in situ hybridization (FISH) has been shown to be a good marker of malignancy in ..
  3. Helgadottir H, Höiom V, Jonsson G, Tuominen R, Ingvar C, Borg A, et al. High risk of tobacco-related cancers in CDKN2A mutation-positive melanoma families. J Med Genet. 2014;51:545-52 pubmed publisher
    ..These cancers were mainly seen in ever-smoking carriers. Germline CDKN2A mutations may confer an increased sensitivity to carcinogens in tobacco smoke. CDKN2A mutation carriers should be counselled to abstain from smoking. ..
  4. Pollice A, Sepe M, Villella V, Tolino F, Vivo M, Calabro V, et al. TBP-1 protects the human oncosuppressor p14ARF from proteasomal degradation. Oncogene. 2007;26:5154-62 pubmed
    ..The mechanisms that regulate alternative reading frame (ARF) turnover have been obscure for long time, being ARF a relatively stable protein...
  5. Kibel A, Jin C, Klim A, Luly J, A Roehl K, Wu W, et al. Association between polymorphisms in cell cycle genes and advanced prostate carcinoma. Prostate. 2008;68:1179-86 pubmed publisher
    ..61: 95% CI=1.05-6.46). These results suggest that in a European-American population, SNPs within cell cycle genes are promising markers for aggressive PCa. Larger studies will be needed to confirm these findings. ..
  6. Schrage Y, Lam S, Jochemsen A, Cleton Jansen A, Taminiau A, Hogendoorn P, et al. Central chondrosarcoma progression is associated with pRb pathway alterations: CDK4 down-regulation and p16 overexpression inhibit cell growth in vitro. J Cell Mol Med. 2009;13:2843-52 pubmed publisher
    ..The aim of this study is to investigate genes involved in cell cycle control: CDK4, CDKN2A/p16, cyclin D1, p21, p53, MDM2 and c-MYC, which may point towards new therapeutic strategies...
  7. Chen Z, Lin Y, Barbieri E, Burlingame S, Hicks J, Ludwig A, et al. Mdm2 deficiency suppresses MYCN-Driven neuroblastoma tumorigenesis in vivo. Neoplasia. 2009;11:753-62 pubmed
    ..of the Mdm2/p53 pathway reveals remarkable p53 stabilization counter-balanced by epigenetic silencing of the p19(Arf) gene in the Mdm2 haploinsufficient tumors...
  8. Romagosa C, Simonetti S, López Vicente L, Mazo A, Lleonart M, Castellvi J, et al. p16(Ink4a) overexpression in cancer: a tumor suppressor gene associated with senescence and high-grade tumors. Oncogene. 2011;30:2087-97 pubmed publisher
    p16(Ink4a) is a protein involved in regulation of the cell cycle. Currently, p16(Ink4a) is considered a tumor suppressor protein because of its physiological role and downregulated expression in a large number of tumors...
  9. Debniak T, Scott R, Masojć B, Serrano Fernandez P, Huzarski T, Byrski T, et al. MC1R common variants, CDKN2A and their association with melanoma and breast cancer risk. Int J Cancer. 2006;119:2597-602 pubmed
    ..The risk of disease seems to be increased additively for patients harbouring also the CDKN2A common variant A148T. ..
  10. Amente S, Gargano B, Diolaiti D, Della Valle G, Lania L, Majello B. p14ARF interacts with N-Myc and inhibits its transcriptional activity. FEBS Lett. 2007;581:821-5 pubmed
    In this study, we report that the human p14(ARF) associates in vivo with the N-Myc and inhibits N-Myc mediated transcriptional activation...
  11. Zeggini E, Scott L, Saxena R, Voight B, Marchini J, Hu T, et al. Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nat Genet. 2008;40:638-45 pubmed publisher
    ..1 x 10(-9)), ADAMTS9 (P = 1.2 x 10(-8)) and NOTCH2 (P = 4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D. ..
  12. Kamb A, Shattuck Eidens D, Eeles R, Liu Q, Gruis N, Ding W, et al. Analysis of the p16 gene (CDKN2) as a candidate for the chromosome 9p melanoma susceptibility locus. Nat Genet. 1994;8:23-6 pubmed
    ..MLM, has been mapped within the same interval on chromosome 9p21 as the gene for a putative cell cycle regulator, p16INK4 (CDKN2) MTS1...
  13. He L, Fan C, Ning X, Feng X, Liu Y, Chen B, et al. Interaction of p14ARF with Brca1 in cancer cell lines and primary breast cancer. Cell Biol Int. 2008;32:1302-9 pubmed publisher
    We report an association between p14ARF and Brca1 in which both proteins co-immunoprecipitate (co-IP) in DU145 cells. The N-terminal 64 residues of p14ARF encoded by exon 1beta are sufficient for this association...
  14. Al Khalaf H, Colak D, Al Saif M, Al Bakheet A, Hendrayani S, Al Yousef N, et al. p16( INK4a) positively regulates cyclin D1 and E2F1 through negative control of AUF1. PLoS ONE. 2011;6:e21111 pubmed publisher
    The cyclin-D/CDK4,6/p16(INK4a)/pRB/E2F pathway, a key regulator of the critical G1 to S phase transition of the cell cycle, is universally disrupted in human cancer...
  15. Holzinger D, Schmitt M, Dyckhoff G, Benner A, Pawlita M, Bosch F. Viral RNA patterns and high viral load reliably define oropharynx carcinomas with active HPV16 involvement. Cancer Res. 2012;72:4993-5003 pubmed publisher
    ..patterns typical for cervical carcinomas (CxCaRNA(+)), and the HPV-targeted tumor suppressor protein p16(INK4a) as markers for HPV infection...
  16. Grarup N, Rose C, Andersson E, Andersen G, Nielsen A, Albrechtsen A, et al. Studies of association of variants near the HHEX, CDKN2A/B, and IGF2BP2 genes with type 2 diabetes and impaired insulin release in 10,705 Danish subjects: validation and extension of genome-wide association studies. Diabetes. 2007;56:3105-11 pubmed publisher
  17. Kriegl L, Neumann J, Vieth M, Greten F, Reu S, Jung A, et al. Up and downregulation of p16(Ink4a) expression in BRAF-mutated polyps/adenomas indicates a senescence barrier in the serrated route to colon cancer. Mod Pathol. 2011;24:1015-22 pubmed publisher
    P16(Ink4a) is an important factor in carcinogenesis and its expression can be linked to oncogene-induced senescence...
  18. Rebouissou S, Hérault A, Letouze E, Neuzillet Y, Laplanche A, Ofualuka K, et al. CDKN2A homozygous deletion is associated with muscle invasion in FGFR3-mutated urothelial bladder carcinoma. J Pathol. 2012;227:315-24 pubmed publisher
  19. Sanchez Aguilera A, Sanchez Beato M, Garcia J, Prieto I, Pollan M, Piris M. p14(ARF) nuclear overexpression in aggressive B-cell lymphomas is a sensor of malfunction of the common tumor suppressor pathways. Blood. 2002;99:1411-8 pubmed
    p14(ARF), the alternative product from the human INK4a/ARF locus, antagonizes Hdm2 and mediates p53 activation in response to oncogenic stimuli...
  20. Gallagher S, Kefford R, Rizos H. Enforced expression of p14ARF induces p53-dependent cell cycle arrest but not apoptosis. Cell Cycle. 2005;4:465-72 pubmed
    Expression of the p14ARF tumour suppressor is induced by hyperproliferative signals produced by RAS, MYC and other oncogenes...
  21. Kwong R, Kalish L, Nguyen T, Kench J, Bova R, Cole I, et al. p14ARF protein expression is a predictor of both relapse and survival in squamous cell carcinoma of the anterior tongue. Clin Cancer Res. 2005;11:4107-16 pubmed
    The INK4A-ARF locus at chromosome 9p21 is frequently altered in head and neck squamous cell carcinoma (SCC) and encodes two distinct tumor suppressors, p16(INK4A) and p14(ARF)...
  22. Scott L, Mohlke K, Bonnycastle L, Willer C, Li Y, Duren W, et al. A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science. 2007;316:1341-5 pubmed
    ..This brings the number of T2D loci now confidently identified to at least 10. ..
  23. Ito S, Ohga T, Saeki H, Watanabe M, Kakeji Y, Morita M, et al. Promoter hypermethylation and quantitative expression analysis of CDKN2A (p14ARF and p16INK4a) gene in esophageal squamous cell carcinoma. Anticancer Res. 2007;27:3345-53 pubmed
    Abnormal hypermethylation of the CDKN2A (p14ARF and p16INK4a) gene can lead to repression of gene expression and contribute to carcinogenesis and tumor progression...
  24. Liu Y, Sanoff H, Cho H, Burd C, Torrice C, Ibrahim J, et al. Expression of p16(INK4a) in peripheral blood T-cells is a biomarker of human aging. Aging Cell. 2009;8:439-48 pubmed publisher
    Expression of the p16(INK4a) tumor suppressor sharply increases with age in most mammalian tissues, and contributes to an age-induced functional decline of certain self-renewing compartments...
  25. Wu X, Gao H, Ke W, Hager M, Xiao S, Freeman M, et al. VentX trans-activates p53 and p16ink4a to regulate cellular senescence. J Biol Chem. 2011;286:12693-701 pubmed publisher
    ..Here, we show that VentX is a direct transcriptional activator of p53-p21 and p16ink4a-Rb tumor suppression pathways...
  26. Cánepa E, Scassa M, Ceruti J, Marazita M, Carcagno A, Sirkin P, et al. INK4 proteins, a family of mammalian CDK inhibitors with novel biological functions. IUBMB Life. 2007;59:419-26 pubmed
    ..The members of INK4 family, comprising p16(INK4a), p15(INK4b), p18(INK4c), and p19(INK4d), block the progression of the cell cycle by binding to either Cdk4 or ..
  27. Novara F, Beri S, Bernardo M, Bellazzi R, Malovini A, Ciccone R, et al. Different molecular mechanisms causing 9p21 deletions in acute lymphoblastic leukemia of childhood. Hum Genet. 2009;126:511-20 pubmed publisher
    ..Among the six cases with heterozygous 9p deletions, we found that the remaining CDKN2A and CDKN2B alleles were hypermethylated at CpG islands. ..
  28. Hu C, Zhang R, Wang C, Wang J, Ma X, Lu J, et al. PPARG, KCNJ11, CDKAL1, CDKN2A-CDKN2B, IDE-KIF11-HHEX, IGF2BP2 and SLC30A8 are associated with type 2 diabetes in a Chinese population. PLoS ONE. 2009;4:e7643 pubmed publisher
    ..0006). The current study confirmed the association between PPARG, KCNJ11, CDKAL1, CDKN2A-CDKN2B, IDE-KIF11-HHEX, IGF2BP2 and SLC30A8 and type 2 diabetes. These type 2 diabetes risk loci contributed to the disease additively. ..
  29. Zhang Y, Sturgis E, Zafereo M, Wei Q, Li G. p14ARF genetic polymorphisms and susceptibility to second primary malignancy in patients with index squamous cell carcinoma of the head and neck. Cancer. 2011;117:1227-35 pubmed publisher
    b>p14(ARF) , an alternate reading frame (ARF) product of the cyclin-dependent kinase inhibitor 2A locus, plays a critical role in crosstalk between the tumor protein 53 (p53) and retinoblastoma (Rb) pathways and in cellular anticancer ..
  30. Dong Y, Wang J, Dong F, Wang X, Zhang Y. The correlations between alteration of p16 gene and clinicopathological factors and prognosis in squamous cell carcinomas of the buccal mucosa. J Oral Pathol Med. 2012;41:463-9 pubmed publisher
    To evaluate relationships between the alteration of p16 gene and the clinical status and prognosis of the patients with squamous cell carcinoma of the buccal mucosa. Thirty buccal cancers were included in the analysis...
  31. Kuo M, den Besten W, Bertwistle D, Roussel M, Sherr C. N-terminal polyubiquitination and degradation of the Arf tumor suppressor. Genes Dev. 2004;18:1862-74 pubmed
    ..p19Arf, although highly basic (22% arginine content), contains only a single lysine residue absent from human p14ARF, and substitution of arginine for lysine in mouse p19Arf had no effect on its rate of degradation...
  32. Kia S, Gorski M, Giannakopoulos S, Verrijzer C. SWI/SNF mediates polycomb eviction and epigenetic reprogramming of the INK4b-ARF-INK4a locus. Mol Cell Biol. 2008;28:3457-64 pubmed publisher
    Stable silencing of the INK4b-ARF-INK4a tumor suppressor locus occurs in a variety of human cancers, including malignant rhabdoid tumors (MRTs)...
  33. Anschau F, Schmitt V, Lambert A, Gonçalves M, Machado D. Transition of cervical carcinoma in situ to invasive cancer: role of p16 INK4a expression in progression and in recurrence. Exp Mol Pathol. 2009;86:46-50 pubmed publisher
    To investigate the expression of p16(INK4a) in cervical carcinoma and its relation to the transition of carcinoma in situ to invasive carcinoma, and its role in recurrence of cervical lesions as well, a series of 90 patients with ..
  34. Huang M, Li H, Nie X, Wu X, Jiang X. An analysis on the combination expression of HPV L1 capsid protein and p16INK4a in cervical lesions. Diagn Cytopathol. 2010;38:573-8 pubmed publisher
    ..The aims of this study were to detect the expression of HPV L1 capsid protein and p16(INK4a) in cervical lesions and to investigate the combination expression of HPV L1 capsid protein and p16(INK4a) in ..
  35. Chen D, Shan J, Zhu W, Qin J, Gu W. Transcription-independent ARF regulation in oncogenic stress-mediated p53 responses. Nature. 2010;464:624-7 pubmed publisher
    The tumour suppressor ARF is specifically required for p53 activation under oncogenic stress...
  36. Clark P, Llanos S, Peters G. Multiple interacting domains contribute to p14ARF mediated inhibition of MDM2. Oncogene. 2002;21:4498-507 pubmed
    The small basic protein p14ARF, encoded by one of the alternative transcripts from the human INK4A/ARF locus, interferes with MDM2-mediated ubiquitination of the p53 tumour suppressor protein...
  37. Goldstein A, Chan M, Harland M, Gillanders E, Hayward N, Avril M, et al. High-risk melanoma susceptibility genes and pancreatic cancer, neural system tumors, and uveal melanoma across GenoMEL. Cancer Res. 2006;66:9818-28 pubmed
    ..in the high-risk melanoma susceptibility genes CDKN2A/alternate reading frames (ARF), which encodes p16 and p14ARF, and CDK4 and to evaluate their relationship with pancreatic cancer (PC), neural system tumors (NST), and uveal ..
  38. Mroz E, Baird A, Michaud W, Rocco J. COOH-terminal binding protein regulates expression of the p16INK4A tumor suppressor and senescence in primary human cells. Cancer Res. 2008;68:6049-53 pubmed publisher
    The p16/pocket-protein pathway sets a balance between tumor suppression and capacity for tissue regeneration...
  39. Lessard F, Morin F, Ivanchuk S, Langlois F, Stefanovsky V, Rutka J, et al. The ARF tumor suppressor controls ribosome biogenesis by regulating the RNA polymerase I transcription factor TTF-I. Mol Cell. 2010;38:539-50 pubmed publisher
    The p14/p19(ARF) (ARF) product of the CDKN2A gene displays tumor suppressor activity both in the presence and absence of p53/TP53...
  40. Lewis J, Thorstad W, Chernock R, Haughey B, Yip J, Zhang Q, et al. p16 positive oropharyngeal squamous cell carcinoma:an entity with a favorable prognosis regardless of tumor HPV status. Am J Surg Pathol. 2010;34:1088-96 pubmed publisher
    ..Many recommend use of both p16 immunohistochemistry and HPV in situ hybridization (ISH)...
  41. Monzon J, Liu L, Brill H, Goldstein A, Tucker M, From L, et al. CDKN2A mutations in multiple primary melanomas. N Engl J Med. 1998;338:879-87 pubmed
    Germ-line mutations in the CDKN2A tumor-suppressor gene (also known as p16, p16INK4a, and MTS1) have been linked to the development of melanoma in some families with inherited melanoma...
  42. Box N, Duffy D, Chen W, Stark M, Martin N, Sturm R, et al. MC1R genotype modifies risk of melanoma in families segregating CDKN2A mutations. Am J Hum Genet. 2001;69:765-73 pubmed
  43. Debniak T, Gorski B, Huzarski T, Byrski T, Cybulski C, Mackiewicz A, et al. A common variant of CDKN2A (p16) predisposes to breast cancer. J Med Genet. 2005;42:763-5 pubmed
    ..8; p = 0.0002). CDKN2A appears to be a low penetrance breast cancer susceptibility gene in Poland. The association should be confirmed in other populations. ..
  44. Kraunz K, Nelson H, Lemos M, Godleski J, Wiencke J, Kelsey K. Homozygous deletion of p16INK4a and tobacco carcinogen exposure in nonsmall cell lung cancer. Int J Cancer. 2006;118:1364-9 pubmed
    Inactivation of p16(INK4a) in the Rb pathway is among the most common somatic alterations observed in nonsmall cell lung cancers (NSCLCs)...
  45. Saxena R, Voight B, Lyssenko V, Burtt N, de Bakker P, Chen H, et al. Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science. 2007;316:1331-6 pubmed
    ..The discovery of associated variants in unsuspected genes and outside coding regions illustrates the ability of genome-wide association studies to provide potentially important clues to the pathogenesis of common diseases. ..
  46. Wang S, Tian C, Xing G, Gao M, Jiao W, Xiao T, et al. ARF-dependent regulation of ATM and p53 associated KZNF (Apak) protein activity in response to oncogenic stress. FEBS Lett. 2010;584:3909-15 pubmed publisher
    ..Here we show that upon oncogene activation, Apak is inhibited in the tumor suppressor ARF-dependent but ATM-independent manner...
  47. Zhang B, Zhu W, Yang P, Liu T, Jiang M, He Z, et al. Cigarette smoking and p16INK4? gene promoter hypermethylation in non-small cell lung carcinoma patients: a meta-analysis. PLoS ONE. 2011;6:e28882 pubmed publisher
    ..Recently, many studies have investigated the association between cigarette smoking and p16(INK4?) gene hypermethylation in lung cancer, but could not reach a unanimous conclusion...
  48. Velimezi G, Liontos M, Vougas K, Roumeliotis T, Bartkova J, Sideridou M, et al. Functional interplay between the DNA-damage-response kinase ATM and ARF tumour suppressor protein in human cancer. Nat Cell Biol. 2013;15:967-77 pubmed publisher
    The DNA damage response (DDR) pathway and ARF function as barriers to cancer development. Although commonly regarded as operating independently of each other, some studies proposed that ARF is positively regulated by the DDR...
  49. Sherborne A, Hosking F, Prasad R, Kumar R, Koehler R, Vijayakrishnan J, et al. Variation in CDKN2A at 9p21.3 influences childhood acute lymphoblastic leukemia risk. Nat Genet. 2010;42:492-4 pubmed publisher
    ..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. ..
  50. Bigot A, Klein A, Gasnier E, Jacquemin V, Ravassard P, Butler Browne G, et al. Large CTG repeats trigger p16-dependent premature senescence in myotonic dystrophy type 1 muscle precursor cells. Am J Pathol. 2009;174:1435-42 pubmed publisher
    ..We demonstrate that an abnormal accumulation of p16 is responsible for this defect because the abolition of p16 activity overcomes early growth arrest and restores an ..
  51. Ye Y, Wang D, Su C, Rong T, Guo A. Combined detection of p53, p16, Rb, and EGFR mutations in lung cancer by suspension microarray. Genet Mol Res. 2009;8:1509-18 pubmed publisher
    Mutations of some contributing factors (p53, p16, Rb, and EGFR) are believed to affect diagnosis and drug resistance of lung cancer...
  52. Vivo M, Di Costanzo A, Fortugno P, Pollice A, Calabrò V, La Mantia G. Downregulation of DeltaNp63alpha in keratinocytes by p14ARF-mediated SUMO-conjugation and degradation. Cell Cycle. 2009;8:3545-51 pubmed
    The tumor suppressor p14(ARF) inhibits cell growth in response to oncogenic stress in a p53-dependent and independent manner. However, new physiologic roles for ARF activation have been proposed...
  53. Randerson Moor J, Harland M, Williams S, Cuthbert Heavens D, Sheridan E, Aveyard J, et al. A germline deletion of p14(ARF) but not CDKN2A in a melanoma-neural system tumour syndrome family. Hum Mol Genet. 2001;10:55-62 pubmed
    ..a family characterized by multiple melanoma and neural cell tumours segregating with a germline deletion of the p14(ARF)-specific exon 1beta of the CDKN2A gene...
  54. Indovina P, Acquaviva A, De Falco G, Rizzo V, Onnis A, Luzzi A, et al. Downregulation and aberrant promoter methylation of p16INK4A: a possible novel heritable susceptibility marker to retinoblastoma. J Cell Physiol. 2010;223:143-50 pubmed publisher
    ..We focused on the p16INK4A tumor suppressor gene because of its possible role in retinoblastoma pathogenesis and its involvement in ..
  55. Harris S, Thorne L, Seaman W, Hayes D, Couch M, Kimple R. Association of p16(INK4a) overexpression with improved outcomes in young patients with squamous cell cancers of the oral tongue. Head Neck. 2011;33:1622-7 pubmed publisher
    ..The aim of this study was to examine biomolecular profiles in a cohort of young adults with squamous cell cancers (SCCs) of the oral tongue...
  56. Soufir N, Avril M, Chompret A, Demenais F, Bombled J, Spatz A, et al. Prevalence of p16 and CDK4 germline mutations in 48 melanoma-prone families in France. The French Familial Melanoma Study Group. Hum Mol Genet. 1998;7:209-16 pubmed
    Germline mutations in the p16 and CDK4 genes have been reported in a subset of melanoma pedigrees, but their prevalence is not well known...
  57. Hallor K, Staaf J, Jonsson G, Heidenblad M, Vult von Steyern F, Bauer H, et al. Frequent deletion of the CDKN2A locus in chordoma: analysis of chromosomal imbalances using array comparative genomic hybridisation. Br J Cancer. 2008;98:434-42 pubmed
  58. Pjanova D, Molven A, Akslen L, Engele L, Streinerte B, Azarjana K, et al. Identification of a CDK4 R24H mutation-positive melanoma family by analysis of early-onset melanoma patients in Latvia. Melanoma Res. 2009;19:119-22 pubmed publisher
    ..This finding supports the proposal that codon 24 is a mutational hotspot in the CDK4 gene. ..
  59. Lukowsky A, Schäfer Hesterberg G, Sterry W, Voit C. Germline CDKN2A/p16 mutations are rare in multiple primary and familial malignant melanoma in German patients. J Dermatol Sci. 2008;49:163-5 pubmed
  60. Lyssenko V, Jonsson A, Almgren P, Pulizzi N, Isomaa B, Tuomi T, et al. Clinical risk factors, DNA variants, and the development of type 2 diabetes. N Engl J Med. 2008;359:2220-32 pubmed publisher
    ..The value of genetic factors increased with an increasing duration of follow-up. ..
  61. Chen X, Barton L, Chi Y, Clurman B, Roberts J. Ubiquitin-independent degradation of cell-cycle inhibitors by the REGgamma proteasome. Mol Cell. 2007;26:843-52 pubmed
    ..The role of REGgamma in cell-cycle regulation may extend beyond p21 regulation, because p16(INK4A) and p19(Arf) also bind to REGgamma and are stabilized in REGgamma-deficient cells.
  62. Turnbull C, Ahmed S, Morrison J, Pernet D, Renwick A, Maranian M, et al. Genome-wide association study identifies five new breast cancer susceptibility loci. Nat Genet. 2010;42:504-7 pubmed publisher
  63. Debniak T, Scott R, Huzarski T, Byrski T, Rozmiarek A, Debniak B, et al. CDKN2A common variants and their association with melanoma risk: a population-based study. Cancer Res. 2005;65:835-9 pubmed
    ..Additional studies are required to confirm whether this particular change is associated with increased risk of other nonmelanoma malignancies. ..
  64. van Hoek M, Dehghan A, Witteman J, van Duijn C, Uitterlinden A, Oostra B, et al. Predicting type 2 diabetes based on polymorphisms from genome-wide association studies: a population-based study. Diabetes. 2008;57:3122-8 pubmed publisher
    ..Combining genetic variants has low predictive value for future type 2 diabetes at a population-based level. The genetic polymorphisms only marginally improved the prediction of type 2 diabetes beyond clinical characteristics. ..
  65. Tong J, Sun X, Cheng H, Zhao D, Ma J, Zhen Q, et al. Expression of p16 in non-small cell lung cancer and its prognostic significance: a meta-analysis of published literatures. Lung Cancer. 2011;74:155-63 pubmed publisher
    The prognostic value of p16 for survival of patients with non-small cell lung cancer (NSCLC) remains controversial. we performed a meta-analysis of the literatures in order to clarify its impact...
  66. Alexander R, Hu Y, Kum J, Montironi R, Lopez Beltran A, MacLennan G, et al. p16 expression is not associated with human papillomavirus in urinary bladder squamous cell carcinoma. Mod Pathol. 2012;25:1526-33 pubmed publisher
    ..the possible role of HPV in the development of squamous cell carcinoma of the urinary bladder and to determine if p16 expression could serve as a surrogate marker for HPV in this malignancy...
  67. Harland M, Meloni R, Gruis N, Pinney E, Brookes S, Spurr N, et al. Germline mutations of the CDKN2 gene in UK melanoma families. Hum Mol Genet. 1997;6:2061-7 pubmed
    Germline mutations in CDKN2 on chromosome 9p21, which codes for the cyclin D kinase inhibitor p16, and more rarely, mutations in the gene coding for CDK4, the protein to which p16 binds, underlie susceptibility in some melanoma families...
  68. Schneider Stock R, Boltze C, Peters B, Höpfner T, Meyer F, Lippert H, et al. Differences in loss of p16INK4 protein expression by promoter methylation between left- and right-sided primary colorectal carcinomas. Int J Oncol. 2003;23:1009-13 pubmed
    The p16INK4 gene, encoding a cyclin-dependent kinase inhibitor, is frequently methylated in colorectal cancer, and a side-specific methylation frequency was suggested...
  69. Kannengiesser C, Avril M, Spatz A, Laud K, Lenoir G, Bressac de Paillerets B. CDKN2A as a uveal and cutaneous melanoma susceptibility gene. Genes Chromosomes Cancer. 2003;38:265-8 pubmed
    ..Immunohistochemistry performed on the UM tissue block revealed loss of CDKN2A protein staining in tumor cells. These observations demonstrate that CDKN2A is also a UM susceptibility gene. ..
  70. Melzer D, Frayling T, Murray A, Hurst A, Harries L, Song H, et al. A common variant of the p16(INK4a) genetic region is associated with physical function in older people. Mech Ageing Dev. 2007;128:370-7 pubmed
    p16(INK4a) is active in cell senescence, ageing and tumor suppression. Deletion of the small p16(INK4a)/ARF/p15(INK4b) region occurs in many cancers...
  71. Hinshelwood R, Melki J, Huschtscha L, Paul C, Song J, Stirzaker C, et al. Aberrant de novo methylation of the p16INK4A CpG island is initiated post gene silencing in association with chromatin remodelling and mimics nucleosome positioning. Hum Mol Genet. 2009;18:3098-109 pubmed publisher
    ..The tumour suppressor gene p16(INK4A) is inactivated in association with CpG island methylation during neoplastic progression in a variety of cancers, ..
  72. Lohrum M, Ashcroft M, Kubbutat M, Vousden K. Contribution of two independent MDM2-binding domains in p14(ARF) to p53 stabilization. Curr Biol. 2000;10:539-42 pubmed
    ..Oncogene activation stabilizes p53 through expression of the ARF protein (p14(ARF) in humans, p19(ARF) in the mouse) [4], and loss of ARF allows tumor development without loss of ..
  73. Herbig U, Jobling W, Chen B, Chen D, Sedivy J. Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21(CIP1), but not p16(INK4a). Mol Cell. 2004;14:501-13 pubmed
    ..These pathways do not affect expression of p16, which was upregulated in a telomere- and DNA damage-independent manner in a subset of cells...
  74. Milyavsky M, Shats I, Cholostoy A, Brosh R, Buganim Y, Weisz L, et al. Inactivation of myocardin and p16 during malignant transformation contributes to a differentiation defect. Cancer Cell. 2007;11:133-46 pubmed
    ..Serum deprivation, intact contact inhibition response, and the p16ink4a/Rb pathway contribute to myocardin induction and differentiation...
  75. O Regan E, Toner M, Finn S, Fan C, Ring M, Hagmar B, et al. p16(INK4A) genetic and epigenetic profiles differ in relation to age and site in head and neck squamous cell carcinomas. Hum Pathol. 2008;39:452-8 pubmed publisher
    ..Functional inactivation of p16 is known to be a common event in HNSCC, mainly by either deletion or methylation...
  76. Usvasalo A, Savola S, Räty R, Vettenranta K, Harila Saari A, Koistinen P, et al. CDKN2A deletions in acute lymphoblastic leukemia of adolescents and young adults: an array CGH study. Leuk Res. 2008;32:1228-35 pubmed publisher
    ..06) to unfavorable biological category. Our results indicate that CDKN2A deletions <200 kb may not be detected by conventional methods. ..
  77. Duesing K, Fatemifar G, Charpentier G, Marre M, Tichet J, Hercberg S, et al. Strong association of common variants in the CDKN2A/CDKN2B region with type 2 diabetes in French Europids. Diabetologia. 2008;51:821-6 pubmed publisher
    ..Further genetic and functional studies are required to identify the aetiological variants at this locus and determine the cellular and physiological mechanisms by which they act to modulate type 2 diabetes susceptibility. ..
  78. Salam I, Hussain S, Mir M, Dar N, Abdullah S, Siddiqi M, et al. Aberrant promoter methylation and reduced expression of p16 gene in esophageal squamous cell carcinoma from Kashmir valley: a high-risk area. Mol Cell Biochem. 2009;332:51-8 pubmed publisher
    ..Inactivation of the p16 gene expression by aberrant promoter methylation plays an important role in the progression of esophageal carcinoma...
  79. Zhang J, Lu A, Li L, Yue J, Lu Y. p16 Modulates VEGF expression via its interaction with HIF-1alpha in breast cancer cells. Cancer Invest. 2010;28:588-97 pubmed publisher
    ..of vascular endothelial growth factor (VEGF), but inversely correlates with the expression of tumor-suppressor gene p16, therefore we examined whether the restoration of p16 in breast cancer cells would modulate VEGF expression...
  80. Ranade K, Hussussian C, Sikorski R, Varmus H, Goldstein A, Tucker M, et al. Mutations associated with familial melanoma impair p16INK4 function. Nat Genet. 1995;10:114-6 pubmed
    ..These complexes are inhibited by low molecular weight proteins, such as p16INK4 (refs 1,2), p15INK4B (ref. 3) and p18 (ref. 4)...
  81. Ferenc T, Lewinski A, Lange D, Niewiadomska H, Sygut J, Sporny S, et al. Analysis of P161NK4A protein expression in follicular thyroid tumors. Pol J Pathol. 2004;55:143-8 pubmed
    ..5% (45/57) and among nodular goiter cases it was 19.3% (13/17). Overexpression of P16INK4A protein was found in 66.7% (8/12) of follicular carcinomas and in 19...
  82. Sinha P, Bahadur S, Thakar A, Matta A, Macha M, Ralhan R, et al. Significance of promoter hypermethylation of p16 gene for margin assessment in carcinoma tongue. Head Neck. 2009;31:1423-30 pubmed publisher
    Loss of p16 expression by promoter hypermethylation has been reported as an early event in the development of oral cancer...
  83. Negrini S, Gorgoulis V, Halazonetis T. Genomic instability--an evolving hallmark of cancer. Nat Rev Mol Cell Biol. 2010;11:220-8 pubmed publisher
    ..encodes p53), ataxia telangiectasia mutated (ATM) and cyclin-dependent kinase inhibitor 2A (CDKN2A; which encodes p16INK4A and p14ARF) support the oncogene-induced DNA replication stress model, which attributes genomic instability and ..
  84. Bohn O, Fuertes Camilo M, Navarro L, Saldivar J, Sanchez Sosa S. p16INK4a expression in basal-like breast carcinoma. Int J Clin Exp Pathol. 2010;3:600-7 pubmed
    ..p16(INK4a) is a tumor suppressor protein, encoded by the CDKN2A gene, which regulates cell cycle...
  85. Lin Z, Gao M, Zhang X, Kim Y, Lee E, Kim H, et al. The hypermethylation and protein expression of p16 INK4A and DNA repair gene O6-methylguanine-DNA methyltransferase in various uterine cervical lesions. J Cancer Res Clin Oncol. 2005;131:364-70 pubmed
    ..study is aimed at investigating the significance of gene promoter methylation status and protein expression of p16 INK4A and O6-methylguanine-DNA methyltransferase (MGMT) in the various uterine cervical lesions...
  86. Kawamoto K, Enokida H, Gotanda T, Kubo H, Nishiyama K, Kawahara M, et al. p16INK4a and p14ARF methylation as a potential biomarker for human bladder cancer. Biochem Biophys Res Commun. 2006;339:790-6 pubmed
    ..We examined whether the methylation status of p16(INK4a) and p14(ARF), genes located upstream of the RB and p53 pathway, is a useful biomarker for the staging, clinical ..
  87. Zhu D, Xu G, Ghandhi S, Hubbard K. Modulation of the expression of p16INK4a and p14ARF by hnRNP A1 and A2 RNA binding proteins: implications for cellular senescence. J Cell Physiol. 2002;193:19-25 pubmed
    ..In this study, we tested whether overexpression of either protein could modulate the mRNA isoforms of the INK4a locus, specifically p14(ARF) and p16(INK4a)...
  88. Freedberg D, Rigas S, Russak J, Gai W, Kaplow M, Osman I, et al. Frequent p16-independent inactivation of p14ARF in human melanoma. J Natl Cancer Inst. 2008;100:784-95 pubmed publisher
    The tumor suppressors p14(ARF) (ARF) and p16(INK4A) (p16) are encoded by overlapping reading frames at the CDKN2A/INK4A locus on chromosome 9p21...
  89. Zuchner S, Gilbert J, Martin E, Leon Guerrero C, Xu P, Browning C, et al. Linkage and association study of late-onset Alzheimer disease families linked to 9p21.3. Ann Hum Genet. 2008;72:725-31 pubmed publisher
    ..003, genotype-PDT p = 0.014). We conclude that CDKN2A is a promising new candidate gene potentially contributing to AD susceptibility on chromosome 9p. ..
  90. Jenkins N, Liu T, Cassidy P, Leachman S, Boucher K, Goodson A, et al. The p16(INK4A) tumor suppressor regulates cellular oxidative stress. Oncogene. 2011;30:265-74 pubmed publisher
    Mutations or deletions in the cyclin-dependent kinase inhibitor p16(INK4A) are associated with multiple cancer types, but are more commonly found in melanoma tumors and associated with familial melanoma predisposition...
  91. Jarmalaite S, Kannio A, Anttila S, Lazutka J, Husgafvel Pursiainen K. Aberrant p16 promoter methylation in smokers and former smokers with nonsmall cell lung cancer. Int J Cancer. 2003;106:913-8 pubmed
    ..We analysed 64 primary lung carcinomas for promoter methylation of the tumour suppressor genes (TSGs) p16 (p16(INK4a)/CDKN2A) and p14 (p14(ARF)) by methylation-specific PCR, in order to evaluate aberrant methylation as a potential ..
  92. Wu M, Cheng Y, Lai J, Hsu M, Chen J, Liu W, et al. Frequent p16INK4a promoter hypermethylation in human papillomavirus-infected female lung cancer in Taiwan. Int J Cancer. 2005;113:440-5 pubmed
    Inactivation of p16INK4a gene through promoter hypermethylation has been frequently observed in non small cell lung cancer; however, various studies have shown a controversial correlation between p16INK4a hypermethylation and cigarette ..