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

Publications161 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. Wang X, Arooz T, Siu W, Chiu C, Lau A, Yamashita K, et al. MDM2 and MDMX can interact differently with ARF and members of the p53 family. FEBS Lett. 2001;490:202-8 pubmed
    ..Finally, we demonstrate that while ARF can interact with MDM2 and inhibit the regulation of p53 by MDM2, no interaction was found between ARF and MDMX...
  5. Yarbrough W, Bessho M, Zanation A, Bisi J, Xiong Y. Human tumor suppressor ARF impedes S-phase progression independent of p53. Cancer Res. 2002;62:1171-7 pubmed
    Using alternative reading frames, the human ARF-INK4a locus encodes two unrelated proteins that both function in tumor suppression...
  6. Haupt A, Guthoff M, Schäfer S, Kirchhoff K, Machicao F, Gallwitz B, et al. The inhibitory effect of recent type 2 diabetes risk loci on insulin secretion is modulated by insulin sensitivity. J Clin Endocrinol Metab. 2009;94:1775-80 pubmed publisher
    ..Effective compensatory mechanisms may exist in subjects with high insulin sensitivity that limit the impact of these genes. ..
  7. Meng S, Luo M, Sun H, Yu X, Shen M, Zhang Q, et al. Identification and characterization of Bmi-1-responding element within the human p16 promoter. J Biol Chem. 2010;285:33219-29 pubmed publisher
    ..One important pathway regulated by Bmi-1 is that involving two cyclin-dependent kinase inhibitors, p16(Ink4a) and p19(Arf), as Bmi-1 represses the INK4a locus on which they are encoded...
  8. Hirai H, Roussel M, Kato J, Ashmun R, Sherr C. Novel INK4 proteins, p19 and p18, are specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6. Mol Cell Biol. 1995;15:2672-81 pubmed
    ..Like the previously described human INK4 polypeptides, p16INK4a/MTS1 and p15INK4b/MTS2, mouse p19 and p18 are primarily composed of tandemly repeated ankyrin motifs, each ca...
  9. Itahana K, Zhang Y. Mitochondrial p32 is a critical mediator of ARF-induced apoptosis. Cancer Cell. 2008;13:542-53 pubmed publisher
    The shared exon 2 of the p14ARF-p16INK4a locus is frequently mutated in human cancers. However, in contrast to the exon 1beta-encoded N-terminal half of ARF, the function of the exon 2-encoded C-terminal half of ARF has been elusive...
  10. Gump J, Stokoe D, McCormick F. Phosphorylation of p16INK4A correlates with Cdk4 association. J Biol Chem. 2003;278:6619-22 pubmed
    ..The tumor suppressor protein p16(INK4A) (p16) forms a complex with Cdk4 and inhibits kinase activity...
  11. Li Q, Wang X, Lu Z, Zhang B, Guan Z, Liu Z, et al. Polycomb CBX7 directly controls trimethylation of histone H3 at lysine 9 at the p16 locus. PLoS ONE. 2010;5:e13732 pubmed publisher
    ..in gastric cancer cell lines MGC803 and BGC823 led to significantly suppress the expression of genes within the p16-Arf-p15 locus. H3K9me3 formation was observed at the p16 promoter and Regulatory Domain (RD)...
  12. Steinestel J, Cronauer M, Muller J, Al Ghazal A, Skowronek P, Arndt A, et al. Overexpression of p16(INK4a) in urothelial carcinoma in situ is a marker for MAPK-mediated epithelial-mesenchymal transition but is not related to human papillomavirus infection. PLoS ONE. 2013;8:e65189 pubmed publisher
    The role of human papillomavirus (HPV) in bladder carcinogenesis remains controversial. Overexpression of p16(INK4a), a surrogate marker for infection with oncogenic HPV in other tumours, has been described for urothelial carcinoma in ..
  13. Hustinx S, Leoni L, Yeo C, Brown P, Goggins M, Kern S, et al. Concordant loss of MTAP and p16/CDKN2A expression in pancreatic intraepithelial neoplasia: evidence of homozygous deletion in a noninvasive precursor lesion. Mod Pathol. 2005;18:959-63 pubmed
    The p16INK4A/CDKN2A (p16) gene on chromosome 9p21 is inactivated in >90% of invasive pancreatic cancers...
  14. Serrano M, Hannon G, Beach D. A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature. 1993;366:704-7 pubmed
    ..Here we report the isolation of a human p16 complementary DNA and demonstrate that p16 binds to CDK4 and inhibits the catalytic activity of the CDK4/cyclin D ..
  15. Shaw R, Liloglou T, Rogers S, Brown J, Vaughan E, Lowe D, et al. Promoter methylation of P16, RARbeta, E-cadherin, cyclin A1 and cytoglobin in oral cancer: quantitative evaluation using pyrosequencing. Br J Cancer. 2006;94:561-8 pubmed
    ..PCR primers were designed to amplify 75-200 bp regions of the CpG rich gene promoters of p16, RARbeta, E-cadherin, cytoglobin and cyclinA1...
  16. Cauchi S, Meyre D, Durand E, Proenca C, Marre M, Hadjadj S, et al. Post genome-wide association studies of novel genes associated with type 2 diabetes show gene-gene interaction and high predictive value. PLoS ONE. 2008;3:e2031 pubmed publisher
    ..Genes expressed in the pancreas interact together and their combined effect dramatically increases the risk for T2D, opening avenues for the development of genetic prediction tests. ..
  17. Ng M, Park K, Oh B, Tam C, Cho Y, Shin H, et al. Implication of genetic variants near TCF7L2, SLC30A8, HHEX, CDKAL1, CDKN2A/B, IGF2BP2, and FTO in type 2 diabetes and obesity in 6,719 Asians. Diabetes. 2008;57:2226-33 pubmed publisher
    ..Our findings support the important but differential contribution of these genetic variants to type 2 diabetes and obesity in Asians compared with Europeans. ..
  18. Kishimoto I, Mitomi H, Ohkura Y, Kanazawa H, Fukui N, Watanabe M. Abnormal expression of p16(INK4a), cyclin D1, cyclin-dependent kinase 4 and retinoblastoma protein in gastric carcinomas. J Surg Oncol. 2008;98:60-6 pubmed publisher
    The p16(INK4a) (p16), cyclin D1, cyclin-dependent kinase (CDK) 4 and retinoblastoma (Rb) genes are components of the Rb pathway that controls the G1-S checkpoint of the cell cycle...
  19. Chauhan G, Spurgeon C, Tabassum R, Bhaskar S, Kulkarni S, Mahajan A, et al. Impact of common variants of PPARG, KCNJ11, TCF7L2, SLC30A8, HHEX, CDKN2A, IGF2BP2, and CDKAL1 on the risk of type 2 diabetes in 5,164 Indians. Diabetes. 2010;59:2068-74 pubmed publisher
    ..Our study replicates the association of well-established common variants with type 2 diabetes in Indians and shows larger effect size for most of them than those reported in Europeans. ..
  20. Kamijo T, Weber J, Zambetti G, Zindy F, Roussel M, Sherr C. Functional and physical interactions of the ARF tumor suppressor with p53 and Mdm2. Proc Natl Acad Sci U S A. 1998;95:8292-7 pubmed
    The INK4a-ARF locus encodes two proteins, p16(INK4a) and p19(ARF), that restrain cell growth by affecting the functions of the retinoblastoma protein and p53, respectively...
  21. Itahana K, Bhat K, Jin A, Itahana Y, Hawke D, Kobayashi R, et al. Tumor suppressor ARF degrades B23, a nucleolar protein involved in ribosome biogenesis and cell proliferation. Mol Cell. 2003;12:1151-64 pubmed
    The tumor suppressor ARF induces a p53-dependent and -independent cell cycle arrest. Unlike the nucleoplasmic MDM2 and p53, ARF localizes in the nucleolus...
  22. Qi Y, Gregory M, Li Z, Brousal J, West K, Hann S. p19ARF directly and differentially controls the functions of c-Myc independently of p53. Nature. 2004;431:712-7 pubmed
    ..progression leads to hyperproliferation and tumorigenesis, it is essential for tumour suppressors, such as p53 and p19ARF (ARF), to curb cell cycle progression in response to increased c-Myc (refs 2, 3)...
  23. Chen J, Li D, Killary A, Sen S, Amos C, Evans D, et al. Polymorphisms of p16, p27, p73, and MDM2 modulate response and survival of pancreatic cancer patients treated with preoperative chemoradiation. Ann Surg Oncol. 2009;16:431-9 pubmed publisher
    ..MDM2 T309G and p16 C580T genotype distributions were significantly different in the patients who underwent PD and those who did not (P ..
  24. Tabara Y, Osawa H, Kawamoto R, Onuma H, Shimizu I, Miki T, et al. Replication study of candidate genes associated with type 2 diabetes based on genome-wide screening. Diabetes. 2009;58:493-8 pubmed publisher
    ..Type 2 diabetes susceptibility of seven candidate genes was confirmed in Japanese. Conservation of susceptible loci for type 2 diabetes was independent of ethnic background. ..
  25. Denton K, Bergeron C, Klement P, Trunk M, Keller T, Ridder R. The sensitivity and specificity of p16(INK4a) cytology vs HPV testing for detecting high-grade cervical disease in the triage of ASC-US and LSIL pap cytology results. Am J Clin Pathol. 2010;134:12-21 pubmed publisher
    We analyzed the performance of p16(INK4a) immunocytochemistry on a series of 810 retrospectively collected atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL) cases with ..
  26. Rocha S, Garrett M, Campbell K, Schumm K, Perkins N. Regulation of NF-kappaB and p53 through activation of ATR and Chk1 by the ARF tumour suppressor. EMBO J. 2005;24:1157-69 pubmed
    The ARF tumour suppressor is a central component of the cellular defence against oncogene activation...
  27. Pascoe L, Frayling T, Weedon M, Mari A, Tura A, Ferrannini E, et al. Beta cell glucose sensitivity is decreased by 39% in non-diabetic individuals carrying multiple diabetes-risk alleles compared with those with no risk alleles. Diabetologia. 2008;51:1989-92 pubmed publisher
    ..001 and p = 0.003, respectively). This study shows how individual type 2 diabetes-risk alleles combine in an additive manner to impact upon pancreatic beta cell function in non-diabetic individuals. ..
  28. Sun P, Nallar S, Raha A, Kalakonda S, Velalar C, Reddy S, et al. GRIM-19 and p16(INK4a) synergistically regulate cell cycle progression and E2F1-responsive gene expression. J Biol Chem. 2010;285:27545-52 pubmed publisher
  29. Medema R, Herrera R, Lam F, Weinberg R. Growth suppression by p16ink4 requires functional retinoblastoma protein. Proc Natl Acad Sci U S A. 1995;92:6289-93 pubmed
    b>p16ink4 has been implicated as a tumor suppressor that is lost from a variety of human tumors and human cell lines. p16ink4 specifically binds and inhibits the cyclin-dependent kinases 4 and 6...
  30. Sugimoto M, Nakamura T, Ohtani N, Hampson L, Hampson I, Shimamoto A, et al. Regulation of CDK4 activity by a novel CDK4-binding protein, p34(SEI-1). Genes Dev. 1999;13:3027-33 pubmed
    The p16(INK4a) tumor suppressor inhibits cyclin-dependent kinases (CDK4 and CDK6). Here we report the isolation of a novel gene, SEI-1, whose product (p34(SEI-1)) appears to antagonize the function of p16(INK4a)...
  31. Lin Y, Diccianni M, Kim Y, Lin H, Lee C, Lin R, et al. Human p16gamma, a novel transcriptional variant of p16(INK4A), coexpresses with p16(INK4A) in cancer cells and inhibits cell-cycle progression. Oncogene. 2007;26:7017-27 pubmed
    The INK4A locus encodes two tumor suppressor genes, p16(INK4A) and p14(ARF), transcribed using alternative exons 1alpha or 1beta spliced onto the same exons 2 and 3...
  32. Gonzalez Navarro H, Abu Nabah Y, Vinue A, Andrés Manzano M, Collado M, Serrano M, et al. p19(ARF) deficiency reduces macrophage and vascular smooth muscle cell apoptosis and aggravates atherosclerosis. J Am Coll Cardiol. 2010;55:2258-68 pubmed publisher
    The goal of this study was to investigate the role in atherosclerosis of the tumor suppressor protein ARF (human p14(ARF), mouse p19(ARF)) encoded by the CDKN2A gene...
  33. Löf Öhlin Z, Sorbe B, Wingren S, Nilsson T. Hypermethylation of promoter regions of the APC1A and p16INK4a genes in relation to prognosis and tumor characteristics in cervical cancer patients. Int J Oncol. 2011;39:683-8 pubmed publisher
    Hypermethylation of the O6-MGMT, p14ARF, p16INK4a, RASSF1A and APC1A genes are unfavourable prognostic markers in colorectal cancer (CRC). We hypothesized that they could be related to prognosis also in cervical cancer...
  34. Fonseca Silva T, Farias L, Cardoso C, Souza L, Carvalho Fraga C, Oliveira M, et al. Analysis of p16(CDKN2A) methylation and HPV-16 infection in oral mucosal dysplasia. Pathobiology. 2012;79:94-100 pubmed publisher
    The purpose of this study was to investigate the relationship between p16(CDKN2A) methylation and epithelial dysplasia (ED). We also evaluated the expressions of proteins related to methylation (DNMT3B and DNMT1)...
  35. McPherson R, Pertsemlidis A, Kavaslar N, Stewart A, Roberts R, Cox D, et al. A common allele on chromosome 9 associated with coronary heart disease. Science. 2007;316:1488-91 pubmed
    ..Homozygotes for the risk allele make up 20 to 25% of Caucasians and have a approximately 30 to 40% increased risk of CHD. ..
  36. Wang X, Feng Y, Xu L, Chen Y, Zhang Y, Su D, et al. YY1 restrained cell senescence through repressing the transcription of p16. Biochim Biophys Acta. 2008;1783:1876-83 pubmed publisher
    ..we demonstrate that YY1 was able to suppress NCI-H460 cell senescence through regulating the expression of p16(INK4a), a cyclin-dependent kinase inhibitor...
  37. Zhao J, Li M, Bradfield J, Wang K, Zhang H, Sleiman P, et al. Examination of type 2 diabetes loci implicates CDKAL1 as a birth weight gene. Diabetes. 2009;58:2414-8 pubmed publisher
    ..Our data show that the same genetic locus that has been identified as a marker for type 2 diabetes in previous studies also influences birth weight. ..
  38. Hashemi J, Platz A, Ueno T, Stierner U, Ringborg U, Hansson J. CDKN2A germ-line mutations in individuals with multiple cutaneous melanomas. Cancer Res. 2000;60:6864-7 pubmed
    ..An in vitro binding assay established that the resulting mutant p16 protein was unable to bind cyclin-dependent kinase 4 and cyclin-dependent kinase 6...
  39. Avbelj M, Hocevar M, Trebusak Podkrajsek K, Krzisnik C, Battelino T. A novel L94Q mutation in the CDKN2A gene in a melanoma kindred. Melanoma Res. 2003;13:567-70 pubmed
    ..The penetrance of the novel mutation was shown to be incomplete. Functional importance of the mutation was assumed from the protein p16 structure.
  40. Berwick M, Orlow I, Hummer A, Armstrong B, Kricker A, Marrett L, et al. The prevalence of CDKN2A germ-line mutations and relative risk for cutaneous malignant melanoma: an international population-based study. Cancer Epidemiol Biomarkers Prev. 2006;15:1520-5 pubmed
    ..The results suggest that the relative risk of mutation carriers in the population may be lower than currently believed and that different mutations on the CDKN2A gene may confer substantially different risks of melanoma. ..
  41. Pascoe L, Tura A, Patel S, Ibrahim I, Ferrannini E, Zeggini E, et al. Common variants of the novel type 2 diabetes genes CDKAL1 and HHEX/IDE are associated with decreased pancreatic beta-cell function. Diabetes. 2007;56:3101-4 pubmed
    ..We confirmed the association between the FTO allele and increased adiposity, but none of the other novel susceptibility alleles were associated with whole-body insulin sensitivity. ..
  42. De Snoo F, Hottenga J, Gillanders E, Sandkuijl L, Jones M, Bergman W, et al. Genome-wide linkage scan for atypical nevi in p16-Leiden melanoma families. Eur J Hum Genet. 2008;16:1135-41 pubmed publisher
    In most Dutch melanoma families, a founder deletion in the melanoma susceptibility gene CDKN2A (which encodes p16) is present. This founder deletion (p16-Leiden) accounts for a significant proportion of the increased melanoma risk...
  43. Nobori T, Miura K, Wu D, Lois A, Takabayashi K, Carson D. Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers. Nature. 1994;368:753-6 pubmed
    ..The CDK4 inhibitor is thought to be a physiological suppressor of proliferation. Cells unable to produce the inhibitor may be prone to neoplastic transformation. ..
  44. Schreiber M, Muller W, Singh G, Graham F. Comparison of the effectiveness of adenovirus vectors expressing cyclin kinase inhibitors p16INK4A, p18INK4C, p19INK4D, p21(WAF1/CIP1) and p27KIP1 in inducing cell cycle arrest, apoptosis and inhibition of tumorigenicity. Oncogene. 1999;18:1663-76 pubmed
    ..Adenovirus vectors were constructed to overexpress cyclin kinase inhibitors p16INK4A, p18INK4C, p19INK4D, p21(WAF1/CIP1) and p27KIP1 under the control of the murine cytomegalovirus immediate early ..
  45. Evangelou K, Bramis J, Peros I, Zacharatos P, Dasiou Plakida D, Kalogeropoulos N, et al. Electron microscopy evidence that cytoplasmic localization of the p16(INK4A) "nuclear" cyclin-dependent kinase inhibitor (CKI) in tumor cells is specific and not an artifact. A study in non-small cell lung carcinomas. Biotech Histochem. 2004;79:5-10 pubmed
    It is well established that p16(INK4A) protein acts as a cell cycle inhibitor in the nucleus. Therefore, cytoplasmic localization of p16 (INK4A) usually is disregarded by investigators as nonspecific...
  46. Brady S, Yu Y, Maggi L, Weber J. ARF impedes NPM/B23 shuttling in an Mdm2-sensitive tumor suppressor pathway. Mol Cell Biol. 2004;24:9327-38 pubmed
    The ARF tumor suppressor is widely regarded as an upstream activator of p53-dependent growth arrest and apoptosis. However, recent findings indicate that ARF can also regulate the cell cycle in the absence of p53...
  47. Wang J, Sasco A, Fu C, Xue H, Guo G, Hua Z, et al. Aberrant DNA methylation of P16, MGMT, and hMLH1 genes in combination with MTHFR C677T genetic polymorphism in esophageal squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev. 2008;17:118-25 pubmed publisher
    To explore the role of aberrant hypermethylation of cancer-related genes, such as P16, MGMT, and hMLH1, in the esophageal squamous cell carcinoma (ESCC) as well as its relation to dietary folate intake and MTHFR C677T polymorphism, we ..
  48. Yin M, Bastacky S, Parwani A, McHale T, Dhir R. p16ink4 immunoreactivity is a reliable marker for urothelial carcinoma in situ. Hum Pathol. 2008;39:527-35 pubmed publisher
    ..Mutations of the cell cycle regulatory gene INK4a (located at 9p21) that encodes p16(INK4) are one of the critical early events in carcinogenesis of UC...
  49. Burd C, Jeck W, Liu Y, Sanoff H, Wang Z, Sharpless N. Expression of linear and novel circular forms of an INK4/ARF-associated non-coding RNA correlates with atherosclerosis risk. PLoS Genet. 2010;6:e1001233 pubmed publisher
    ..Although this locus encodes three well-characterized tumor suppressors, p16(INK4a), p15(INK4b), and ARF, the SNPs most strongly associated with ASVD are ?120 kb from the nearest coding gene within ..
  50. Sakano S, Berggren P, Kumar R, Steineck G, Adolfsson J, Onelov E, et al. Clinical course of bladder neoplasms and single nucleotide polymorphisms in the CDKN2A gene. Int J Cancer. 2003;104:98-103 pubmed
    ..Further, the results indicate, a role for the 3' UTR polymorphisms in the CDKN2A gene in tumor invasiveness. ..
  51. Pollice A, Nasti V, Ronca R, Vivo M, Lo Iacono M, Calogero R, et al. Functional and physical interaction of the human ARF tumor suppressor with Tat-binding protein-1. J Biol Chem. 2004;279:6345-53 pubmed
    The p14ARF tumor suppressor is a key regulator of cellular proliferation, frequently inactivated in human cancer, whose mode of action is currently not completely understood...
  52. Liu Y, Lan Q, Siegfried J, Luketich J, Keohavong P. Aberrant promoter methylation of p16 and MGMT genes in lung tumors from smoking and never-smoking lung cancer patients. Neoplasia. 2006;8:46-51 pubmed
    ..we applied methylation-specific polymerase chain reaction to compare the frequencies of the methylated promoter of p16 and O6-methylguanine-DNA methyltransferase (MGMT) genes in lung tumors from 122 patients with non-small cell lung ..
  53. Lal A, Kim H, Abdelmohsen K, Kuwano Y, Pullmann R, Srikantan S, et al. p16(INK4a) translation suppressed by miR-24. PLoS ONE. 2008;3:e1864 pubmed publisher
    Expression of the tumor suppressor p16(INK4a) increases during aging and replicative senescence. Here, we report that the microRNA miR-24 suppresses p16 expression in human diploid fibroblasts and cervical carcinoma cells...
  54. Irelan J, Gutierrez Del Arroyo A, Gutierrez A, Peters G, Quon K, Miraglia L, et al. A functional screen for regulators of CKDN2A reveals MEOX2 as a transcriptional activator of INK4a. PLoS ONE. 2009;4:e5067 pubmed publisher
    The CDKN2A locus encodes two important tumor suppressors, INK4a and ARF, which respond to oncogenic stresses by inducing cellular senescence...
  55. Hoffmann M, Ihloff A, Görögh T, Weise J, Fazel A, Krams M, et al. p16(INK4a) overexpression predicts translational active human papillomavirus infection in tonsillar cancer. Int J Cancer. 2010;127:1595-602 pubmed publisher
    ..feedback mechanisms, the pRb inactivation causes an increase of the inhibitor of the cyclin-dependent kinases p16(INK4a)...
  56. El Messaoudi Aubert S, Nicholls J, Maertens G, Brookes S, Bernstein E, Peters G. Role for the MOV10 RNA helicase in polycomb-mediated repression of the INK4a tumor suppressor. Nat Struct Mol Biol. 2010;17:862-8 pubmed publisher
    ..Small hairpin RNA (shRNA)-mediated knockdown of MOV10 in human fibroblasts leads to the upregulation of the INK4a tumor suppressor, a known target of PcG-mediated repression, accompanied by the dissociation of PRC1 proteins from ..
  57. Kamb A, Gruis N, Weaver Feldhaus J, Liu Q, Harshman K, Tavtigian S, et al. A cell cycle regulator potentially involved in genesis of many tumor types. Science. 1994;264:436-40 pubmed
    ..This region contained a gene, Multiple Tumor Suppressor 1 (MTS1), that encodes a previously identified inhibitor (p16) of cyclin-dependent kinase 4...
  58. Bertram C, Gaut R, Barrett J, Pinney E, Whitaker L, Turner F, et al. An assessment of the CDKN2A variant Ala148Thr as a nevus/melanoma susceptibility allele. J Invest Dermatol. 2002;119:961-5 pubmed
    ..5 nevi in those without, p = 0.02). After allowing for potential confounders this was not evident in the population-based sample...
  59. Bernard D, Martinez Leal J, Rizzo S, Martinez D, Hudson D, Visakorpi T, et al. CBX7 controls the growth of normal and tumor-derived prostate cells by repressing the Ink4a/Arf locus. Oncogene. 2005;24:5543-51 pubmed
    ..Ablation of CBX7 expression using short hairpin RNAs (shRNA) resulted in upregulation of p16Ink4a and p14Arf in both LNCaP and PC-3 prostate cell lines...
  60. Zhang Z, Rosen D, Yao J, Huang J, Liu J. Expression of p14ARF, p15INK4b, p16INK4a, and DCR2 increases during prostate cancer progression. Mod Pathol. 2006;19:1339-43 pubmed
    ..p14(ARF), p15(INK4b), and p16(INK4a), which are known to regulate G1 cell cycle arrest, and the tumor necrosis factor receptor superfamily member ..
  61. Shima K, Nosho K, Baba Y, Cantor M, Meyerhardt J, Giovannucci E, et al. Prognostic significance of CDKN2A (p16) promoter methylation and loss of expression in 902 colorectal cancers: Cohort study and literature review. Int J Cancer. 2011;128:1080-94 pubmed publisher
    A cyclin-dependent kinase inhibitor CDKN2A (p16/Ink4a) is a tumor suppressor and upregulated in cellular senescence...
  62. Vasen H, Wasser M, van Mil A, Tollenaar R, Konstantinovski M, Gruis N, et al. Magnetic resonance imaging surveillance detects early-stage pancreatic cancer in carriers of a p16-Leiden mutation. Gastroenterology. 2011;140:850-6 pubmed publisher
    ..Individuals with germline mutations in p16-Leiden have a lifetime risk of 15% to 20% of developing pancreatic cancer...
  63. Svensson S, Nilsson K, Ringberg A, Landberg G. Invade or proliferate? Two contrasting events in malignant behavior governed by p16(INK4a) and an intact Rb pathway illustrated by a model system of basal cell carcinoma. Cancer Res. 2003;63:1737-42 pubmed
    ..in infiltrative cells were surprising and clearly indicated that invasion in tumors with an intact p16(INK4a)-cyclin D-retinoblastoma protein (Rb) pathway was equivalent to ceased proliferation...
  64. Cui X, Shirai Y, Wakai T, Yokoyama N, Hirano S, Hatakeyama K. Aberrant expression of pRb and p16(INK4), alone or in combination, indicates poor outcome after resection in patients with colorectal carcinoma. Hum Pathol. 2004;35:1189-95 pubmed
    This study aimed to identify potential abnormalities of retinoblastoma protein (pRb) and p16(INK4a) (p16) expression in resectable colorectal carcinomas (CRCs) and to assess the prognostic significance of pRb and p16 levels in patients ..
  65. Rizos H, McKenzie H, Ayub A, Woodruff S, Becker T, Scurr L, et al. Physical and functional interaction of the p14ARF tumor suppressor with ribosomes. J Biol Chem. 2006;281:38080-8 pubmed
    Alterations in the p14(ARF) tumor suppressor are frequent in many human cancers and are associated with susceptibility to melanoma, pancreatic cancer, and nervous system tumors...
  66. Bracken A, Kleine Kohlbrecher D, Dietrich N, Pasini D, Gargiulo G, Beekman C, et al. The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells. Genes Dev. 2007;21:525-30 pubmed
    The p16INK4A and p14ARF proteins, encoded by the INK4A-ARF locus, are key regulators of cellular senescence, yet the mechanisms triggering their up-regulation are not well understood...
  67. FitzGerald M, Harkin D, Silva Arrieta S, MacDonald D, Lucchina L, Unsal H, et al. Prevalence of germ-line mutations in p16, p19ARF, and CDK4 in familial melanoma: analysis of a clinic-based population. Proc Natl Acad Sci U S A. 1996;93:8541-5 pubmed
    ..We screened for germ-line mutations in p16 and in two other candidate melanoma genes, p19ARF and CDK4, in 33 consecutive patients treated for melanoma; these patients had at least one affected first or ..
  68. Hemmati P, Gillissen B, von Haefen C, Wendt J, Stärck L, Güner D, et al. Adenovirus-mediated overexpression of p14(ARF) induces p53 and Bax-independent apoptosis. Oncogene. 2002;21:3149-61 pubmed
    The human INK4a gene locus encodes two structurally unrelated tumor suppressor proteins, p16(INK4a) and p14(ARF), which are frequently inactivated in human cancer...
  69. Kitagawa Y, Inoue K, Sasaki S, Hayashi Y, Matsuo Y, Lieber M, et al. Prevalent involvement of illegitimate V(D)J recombination in chromosome 9p21 deletions in lymphoid leukemia. J Biol Chem. 2002;277:46289-97 pubmed
    To understand molecular pathways underlying 9p21 deletions, which lead to inactivation of the p16/CDKN2A, p14/ARF, and/or p15/CDKN2B genes, in lymphoid leukemia, 30 breakpoints were cloned from 15 lymphoid leukemia cell lines...
  70. Lamperska K, Karezewska A, Kwiatkowska E, Mackiewicz A. Analysis of mutations in the p16/CDKN2A gene in sporadic and familial melanoma in the Polish population. Acta Biochim Pol. 2002;49:369-76 pubmed
  71. Oldenburg R, de Vos tot Nederveen Cappel W, van Puijenbroek M, van den Ouweland A, Bakker E, Griffioen G, et al. Extending the p16-Leiden tumour spectrum by respiratory tract tumours. J Med Genet. 2004;41:e31 pubmed
  72. Kiss N, Geli J, Lundberg F, Avci C, Velazquez Fernandez D, Hashemi J, et al. Methylation of the p16INK4A promoter is associated with malignant behavior in abdominal extra-adrenal paragangliomas but not pheochromocytomas. Endocr Relat Cancer. 2008;15:609-21 pubmed publisher
    ..Studies in animal models have shown that inactivation of the products of the cyclin dependent kinase inhibitor 2A (CDKN2A) gene locus, p16INK4A and p14ARF, promotes the development of pheochromocytoma, especially ..
  73. Herder C, Rathmann W, Strassburger K, Finner H, Grallert H, Huth C, et al. Variants of the PPARG, IGF2BP2, CDKAL1, HHEX, and TCF7L2 genes confer risk of type 2 diabetes independently of BMI in the German KORA studies. Horm Metab Res. 2008;40:722-6 pubmed publisher
    ..We conclude that gene variants of CDKAL1, PPARG, IGF2BP2, HHEX, TCF7L2, and FTO predispose to type 2 diabetes in the German KORA 500 K study population. These associations appear to be independent of BMI. ..
  74. Goode E, Fridley B, Vierkant R, Cunningham J, Phelan C, Anderson S, et al. Candidate gene analysis using imputed genotypes: cell cycle single-nucleotide polymorphisms and ovarian cancer risk. Cancer Epidemiol Biomarkers Prev. 2009;18:935-44 pubmed publisher
    ..These results exemplify the utility of imputation in candidate gene studies and lend evidence to a role of cell cycle genes in ovarian cancer etiology, suggest a reduced set of SNPs to target in additional cases and controls. ..
  75. Cubilla A, Lloveras B, Alejo M, Clavero O, Chaux A, Kasamatsu E, et al. Value of p16(INK)?(a) in the pathology of invasive penile squamous cell carcinomas: A report of 202 cases. Am J Surg Pathol. 2011;35:253-61 pubmed publisher
    ..In this study, we evaluated p16(INK)?(a) immunohistochemical expression, which is simpler and less costly, as a potential marker of high-risk HPV (..
  76. Mukherjee B, DeLancey J, Raskin L, Everett J, Jeter J, Begg C, et al. Risk of non-melanoma cancers in first-degree relatives of CDKN2A mutation carriers. J Natl Cancer Inst. 2012;104:953-6 pubmed publisher
    ..0% by age 85 years (95% CI = 39.0% to 75.4%) by the kin-cohort method, under the standard assumptions of Mendelian genetics on the genotype distribution of FDRs conditional on proband genotype. ..
  77. Hearle N, Damato B, Humphreys J, Wixey J, Green H, Stone J, et al. Contribution of germline mutations in BRCA2, P16(INK4A), P14(ARF) and P15 to uveal melanoma. Invest Ophthalmol Vis Sci. 2003;44:458-62 pubmed
    ..cutaneous and uveal melanomas in some families, coupled with the high frequency of somatic deletions of the INK4A-ARF locus in uveal melanomas, strongly suggests that mutations in P16(INK4A) and P15 account for a proportion of ..
  78. Ausserlechner M, Obexer P, Geley S, Kofler R. G1 arrest by p16INK4A uncouples growth from cell cycle progression in leukemia cells with deregulated cyclin E and c-Myc expression. Leukemia. 2005;19:1051-7 pubmed
    The cell cycle inhibitor p16(INK4A) is frequently inactivated in acute lymphoblastic T-cell leukemia (T-ALL). We analyzed mechanisms and consequences of p16(INK4A) reconstitution in T-ALL cells lacking this tumor suppressor...
  79. Komori H, Enomoto M, Nakamura M, Iwanaga R, Ohtani K. Distinct E2F-mediated transcriptional program regulates p14ARF gene expression. EMBO J. 2005;24:3724-36 pubmed
    The tumor suppressor p14(ARF) gene is induced by ectopically expressed E2F, a positive regulator of the cell cycle. The gene is expressed at low levels in normally growing cells in contrast to high levels in varieties of tumors...
  80. Horn L, Reichert A, Oster A, Arndal S, Trunk M, Ridder R, et al. Immunostaining for p16INK4a used as a conjunctive tool improves interobserver agreement of the histologic diagnosis of cervical intraepithelial neoplasia. Am J Surg Pathol. 2008;32:502-12 pubmed publisher
    ..Overexpression of the cyclin-dependent kinase inhibitor p16INK4a, a cell cycle regulating protein, has been shown to be strongly correlated with dysplastic lesions of the cervix ..
  81. Magnusson S, Borg A, Kristoffersson U, Nilbert M, Wiebe T, Olsson H. Higher occurrence of childhood cancer in families with germline mutations in BRCA2, MMR and CDKN2A genes. Fam Cancer. 2008;7:331-7 pubmed publisher
    ..5-44.1), MMR genes (OR 29.0; 95% CI 9.1-92.6), and CDKN2A (OR 30.2; 95% CI 7.0-131.1). This study suggests that the risk for childhood tumors is increased in families with germline mutations in the BRCA2, MMR and CDKN2A genes. ..
  82. McKeown P, Merlini P, Berzuini C, Bernardinelli L, Peyvandi F, Tubaro M, et al. Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants. Nat Genet. 2009;41:334-41 pubmed publisher
    ..SNPs at nine loci were reproducibly associated with myocardial infarction, but tests of common and rare CNVs failed to identify additional associations with myocardial infarction risk. ..
  83. Poetsch M, Hemmerich M, Kakies C, Kleist B, Wolf E, vom Dorp F, et al. Alterations in the tumor suppressor gene p16(INK4A) are associated with aggressive behavior of penile carcinomas. Virchows Arch. 2011;458:221-9 pubmed publisher
    ..The carcinomas were analyzed for allelic loss (LOH) in p16(INK4A) and p53, as well as for mutations in the p16(INK4A) and the p53 gene...
  84. Sterlacci W, Tzankov A, Veits L, Zelger B, Bihl M, Foerster A, et al. A comprehensive analysis of p16 expression, gene status, and promoter hypermethylation in surgically resected non-small cell lung carcinomas. J Thorac Oncol. 2011;6:1649-57 pubmed publisher
    The role of p16 is gaining importance in non-small cell lung cancer (NSCLC) because of epigenetic therapy options...