Gene Review:
CDKN2A - cyclin-dependent kinase inhibitor 2A
Homo sapiens
Synonyms:
ARF, CDK4I, CDKN2, CMM2, INK4, ...
Shannon,
Santin,
Mann,
Lechner,
Nielsen,
Johnston,
Stidley,
Chidambaram,
Roman,
Thomas,
Burnett,
Struewing,
Louis,
Anfossi,
Kazianis,
Rizos,
Moots,
Bellone,
Indsto,
Rosenberg,
Goldstein,
Shaughnessy,
Morizot,
Kefford,
Belinsky,
Bignotti,
Tian,
Osterndorff,
Palmieri,
Siegel,
Cannon,
Pecorelli,
Nairn,
N.B. Kiss,
J. Geli,
F. Lundberg,
C. Avci,
D. Velazquez-Fernandez,
J. Hashemi,
G. Weber,
A. Höög,
T.J. Ekström,
M. Bäckdahl,
C. Larsson,
Grimes,
Crooks,
O'Brien,
Fraser,
Tucker,
Burns,
Coletta,
Cané,
Kay,
Zhan,
Smith,
Divine,
Crowell,
Darmanian,
Winters,
Palmisano,
Gilliland,
Tellez,
Harms,
- Mutation of the CDKN2A 5' UTR creates an aberrant initiation codon and predisposes to melanoma. Liu, L., Dilworth, D., Gao, L., Monzon, J., Summers, A., Lassam, N., Hogg, D. Nat. Genet. (1999)
- High frequency of multiple melanomas and breast and pancreas carcinomas in CDKN2A mutation-positive melanoma families. Borg, A., Sandberg, T., Nilsson, K., Johannsson, O., Klinker, M., Måsbäck, A., Westerdahl, J., Olsson, H., Ingvar, C. J. Natl. Cancer Inst. (2000)
- Genotype-phenotype relationships in U.S. melanoma-prone families with CDKN2A and CDK4 mutations. Goldstein, A.M., Struewing, J.P., Chidambaram, A., Fraser, M.C., Tucker, M.A. J. Natl. Cancer Inst. (2000)
- Intragenic mutations of CDKN2B and CDKN2A in primary human esophageal cancers. Suzuki, H., Zhou, X., Yin, J., Lei, J., Jiang, H.Y., Suzuki, Y., Chan, T., Hannon, G.J., Mergner, W.J., Abraham, J.M. Hum. Mol. Genet. (1995)
- Aurora-A and p16 polymorphisms contribute to an earlier age at diagnosis of pancreatic cancer in Caucasians. Chen, J., Li, D., Wei, C., Sen, S., Killary, A.M., Amos, C.I., Evans, D.B., Abbruzzese, J.L., Frazier, M.L. Clin. Cancer Res. (2007)
- Methylation of the p16INK4A promoter is associated with malignant behavior in abdominal extra-adrenal paragangliomas but not pheochromocytomas. Kiss, N.B., Geli, J., Lundberg, F., Avci, C., Velazquez-Fernandez, D., Hashemi, J., Weber, G., Höög, A., Ekström, T.J., Bäckdahl, M., Larsson, C. Endocr. Relat. Cancer (2008)
- Neuronal expression of cycline dependent kinase inhibitors of the INK4 family in Alzheimer's disease. Arendt, T., Holzer, M., Gärtner, U. Journal of neural transmission (Vienna, Austria : 1996) (1998)
- Promotor hypermethylation of p14ARF is a key alteration for progression of oral squamous cell carcinoma. Ishida, E., Nakamura, M., Ikuta, M., Shimada, K., Matsuyoshi, S., Kirita, T., Konishi, N. Oral Oncol. (2005)
- Role for PP2A in ARF signaling to p53. Moule, M.G., Collins, C.H., McCormick, F., Fried, M. Proc. Natl. Acad. Sci. U.S.A. (2004)
- Aberrant promoter methylation in bronchial epithelium and sputum from current and former smokers. Belinsky, S.A., Palmisano, W.A., Gilliland, F.D., Crooks, L.A., Divine, K.K., Winters, S.A., Grimes, M.J., Harms, H.J., Tellez, C.S., Smith, T.M., Moots, P.P., Lechner, J.F., Stidley, C.A., Crowell, R.E. Cancer Res. (2002)
- Induction of Id1 and Id3 by latent membrane protein 1 of Epstein-Barr virus and regulation of p27/Kip and cyclin-dependent kinase 2 in rodent fibroblast transformation. Everly, D.N., Mainou, B.A., Raab-Traub, N. J. Virol. (2004)
- The Regulation of INK4/ARF in Cancer and Aging. Kim, W.Y., Sharpless, N.E. Cell (2006)
- Use of human tissue to assess the oncogenic activity of melanoma-associated mutations. Chudnovsky, Y., Adams, A.E., Robbins, P.B., Lin, Q., Khavari, P.A. Nat. Genet. (2005)
- Fusion of NUP214 to ABL1 on amplified episomes in T-cell acute lymphoblastic leukemia. Graux, C., Cools, J., Melotte, C., Quentmeier, H., Ferrando, A., Levine, R., Vermeesch, J.R., Stul, M., Dutta, B., Boeckx, N., Bosly, A., Heimann, P., Uyttebroeck, A., Mentens, N., Somers, R., MacLeod, R.A., Drexler, H.G., Look, A.T., Gilliland, D.G., Michaux, L., Vandenberghe, P., Wlodarska, I., Marynen, P., Hagemeijer, A. Nat. Genet. (2004)
- DNMT1 is required to maintain CpG methylation and aberrant gene silencing in human cancer cells. Robert, M.F., Morin, S., Beaulieu, N., Gauthier, F., Chute, I.C., Barsalou, A., MacLeod, A.R. Nat. Genet. (2003)
- Multiple tumor suppressor pathways negatively regulate telomerase. Lin, S.Y., Elledge, S.J. Cell (2003)
- CDKN2A germ-line mutations in individuals with multiple cutaneous melanomas. Hashemi, J., Platz, A., Ueno, T., Stierner, U., Ringborg, U., Hansson, J. Cancer Res. (2000)
- Overexpression of a fish CDKN2 gene in a hereditary melanoma model. Kazianis, S., Coletta, L.D., Morizot, D.C., Johnston, D.A., Osterndorff, E.A., Nairn, R.S. Carcinogenesis (2000)
- Infrequent methylation of CDKN2A(MTS1/p16) and rare mutation of both CDKN2A and CDKN2B(MTS2/p15) in primary astrocytic tumours. Schmidt, E.E., Ichimura, K., Messerle, K.R., Goike, H.M., Collins, V.P. Br. J. Cancer (1997)
- Cloning and characterization of the CDKN2A and p19ARF genes from Monodelphis domestica. Sherburn, T.E., Gale, J.M., Ley, R.D. DNA Cell Biol. (1998)
- The role of p16 in the E2F-dependent thymidine kinase regulation. Hengstschläger, M., Hengstschläger-Ottnad, E., Pusch, O., Wawra, E. Oncogene (1996)
- Evolution of neoplastic cell lineages in Barrett oesophagus. Barrett, M.T., Sanchez, C.A., Prevo, L.J., Wong, D.J., Galipeau, P.C., Paulson, T.G., Rabinovitch, P.S., Reid, B.J. Nat. Genet. (1999)
- INK4a-deficient human diploid fibroblasts are resistant to RAS-induced senescence. Brookes, S., Rowe, J., Ruas, M., Llanos, S., Clark, P.A., Lomax, M., James, M.C., Vatcheva, R., Bates, S., Vousden, K.H., Parry, D., Gruis, N., Smit, N., Bergman, W., Peters, G. EMBO J. (2002)
- CDKN2A/p16 is inactivated in most melanoma cell lines. Castellano, M., Pollock, P.M., Walters, M.K., Sparrow, L.E., Down, L.M., Gabrielli, B.G., Parsons, P.G., Hayward, N.K. Cancer Res. (1997)
- Tbx2 is overexpressed and plays an important role in maintaining proliferation and suppression of senescence in melanomas. Vance, K.W., Carreira, S., Brosch, G., Goding, C.R. Cancer Res. (2005)
- CDKN2A gene deletions and loss of p16 expression occur in osteosarcomas that lack RB alterations. Nielsen, G.P., Burns, K.L., Rosenberg, A.E., Louis, D.N. Am. J. Pathol. (1998)
- Increased expression of unmethylated CDKN2D by 5-aza-2'-deoxycytidine in human lung cancer cells. Zhu, W.G., Dai, Z., Ding, H., Srinivasan, K., Hall, J., Duan, W., Villalona-Calero, M.A., Plass, C., Otterson, G.A. Oncogene (2001)
- Gene expression profiles of primary HPV16- and HPV18-infected early stage cervical cancers and normal cervical epithelium: identification of novel candidate molecular markers for cervical cancer diagnosis and therapy. Santin, A.D., Zhan, F., Bignotti, E., Siegel, E.R., Cané, S., Bellone, S., Palmieri, M., Anfossi, S., Thomas, M., Burnett, A., Kay, H.H., Roman, J.J., O'Brien, T.J., Tian, E., Cannon, M.J., Shaughnessy, J., Pecorelli, S. Virology (2005)
- Serial studies of methylation of CDKN2B and CDKN2A in relapsed acute promyelocytic leukaemia treated with arsenic trioxide. Au, W.Y., Fung, A.T., Ma, E.S., Chan, C.H., Wong, K.F., Chim, C.S., Liang, R.H., Kwong, Y.L. Br. J. Haematol. (2005)
- The prognostic significance of CDKN2A, CDKN2B and MTAP inactivation in B-lineage acute lymphoblastic leukemia of childhood. Results of the EORTC studies 58881 and 58951. Mirebeau, D., Acquaviva, C., Suciu, S., Bertin, R., Dastugue, N., Robert, A., Boutard, P., Méchinaud, F., Plouvier, E., Otten, J., Vilmer, E., Cavé, H. Haematologica (2006)
- Morphologically normal-appearing mammary epithelial cells obtained from high-risk women exhibit methylation silencing of INK4a/ARF. Bean, G.R., Bryson, A.D., Pilie, P.G., Goldenberg, V., Baker, J.C., Ibarra, C., Brander, D.M., Paisie, C., Case, N.R., Gauthier, M., Reynolds, P.A., Dietze, E., Ostrander, J., Scott, V., Wilke, L.G., Yee, L., Kimler, B.F., Fabian, C.J., Zalles, C.M., Broadwater, G., Tlsty, T.D., Seewaldt, V.L. Clin. Cancer Res. (2007)
- ARF promotes MDM2 degradation and stabilizes p53: ARF-INK4a locus deletion impairs both the Rb and p53 tumor suppression pathways. Zhang, Y., Xiong, Y., Yarbrough, W.G. Cell (1998)
- Lack of cyclin D-Cdk complexes in Rb-negative cells correlates with high levels of p16INK4/MTS1 tumour suppressor gene product. Parry, D., Bates, S., Mann, D.J., Peters, G. EMBO J. (1995)
- Cyclin E, a redundant cyclin in breast cancer. Gray-Bablin, J., Zalvide, J., Fox, M.P., Knickerbocker, C.J., DeCaprio, J.A., Keyomarsi, K. Proc. Natl. Acad. Sci. U.S.A. (1996)
- Disruption of the cyclin D/cyclin-dependent kinase/INK4/retinoblastoma protein regulatory pathway in human neuroblastoma. Easton, J., Wei, T., Lahti, J.M., Kidd, V.J. Cancer Res. (1998)
- Concordant loss of MTAP and p16/CDKN2A expression in gastroesophageal carcinogenesis: evidence of homozygous deletion in esophageal noninvasive precursor lesions and therapeutic implications. Powell, E.L., Leoni, L.M., Canto, M.I., Forastiere, A.A., Iocobuzio-Donahue, C.A., Wang, J.S., Maitra, A., Montgomery, E. Am. J. Surg. Pathol. (2005)
- Multiple abnormalities of the p16INK4a-pRb regulatory pathway in cultured melanoma cells. Rizos, H., Darmanian, A.P., Indsto, J.O., Shannon, J.A., Kefford, R.F., Mann, G.J. Melanoma Res. (1999)
- Caspase 3 specifically cleaves p21WAF1/CIP1 in the earlier stage of apoptosis in SK-HEP-1 human hepatoma cells. Park, J.A., Kim, K.W., Kim, S.I., Lee, S.K. Eur. J. Biochem. (1998)
- Molecular genetic analysis of phosphatase and tensin homolog and p16 tumor suppressor genes in patients with malignant glioma. Abdullah, J.M., Zainuddin, N., Sulong, S., Jaafar, H., Isa, M.N. Neurosurgical focus [electronic resource]. (2003)
- Different effects of p14ARF on the levels of ubiquitinated p53 and Mdm2 in vivo. Xirodimas, D., Saville, M.K., Edling, C., Lane, D.P., Laín, S. Oncogene (2001)
- Mutations in human ARF exon 2 disrupt its nucleolar localization and impair its ability to block nuclear export of MDM2 and p53. Zhang, Y., Xiong, Y. Mol. Cell (1999)
- Distinct E2F-mediated transcriptional program regulates p14ARF gene expression. Komori, H., Enomoto, M., Nakamura, M., Iwanaga, R., Ohtani, K. EMBO J. (2005)
- Inhibition of cyclin D-CDK4/CDK6 activity is associated with an E2F-mediated induction of cyclin kinase inhibitor activity. Khleif, S.N., DeGregori, J., Yee, C.L., Otterson, G.A., Kaye, F.J., Nevins, J.R., Howley, P.M. Proc. Natl. Acad. Sci. U.S.A. (1996)
- The human ARF cell cycle regulatory gene promoter is a CpG island which can be silenced by DNA methylation and down-regulated by wild-type p53. Robertson, K.D., Jones, P.A. Mol. Cell. Biol. (1998)
- Structural basis for inhibition of the cyclin-dependent kinase Cdk6 by the tumour suppressor p16INK4a. Russo, A.A., Tong, L., Lee, J.O., Jeffrey, P.D., Pavletich, N.P. Nature (1998)
- Aberrant expression of G1-phase cell cycle regulators in flat and exophytic adenomas of the human colon. Bartkova, J., Thullberg, M., Slezak, P., Jaramillo, E., Rubio, C., Thomassen, L.H., Bartek, J. Gastroenterology (2001)
- Involvement of the cyclin-dependent kinase inhibitor p16 (INK4a) in replicative senescence of normal human fibroblasts. Alcorta, D.A., Xiong, Y., Phelps, D., Hannon, G., Beach, D., Barrett, J.C. Proc. Natl. Acad. Sci. U.S.A. (1996)
- Frequent inactivation of CDKN2A and rare mutation of TP53 in PCNSL. Cobbers, J.M., Wolter, M., Reifenberger, J., Ring, G.U., Jessen, F., An, H.X., Niederacher, D., Schmidt, E.E., Ichimura, K., Floeth, F., Kirsch, L., Borchard, F., Louis, D.N., Collins, V.P., Reifenberger, G. Brain Pathol. (1998)
- Patterns of CDKN2A gene loss in sequential oral epithelial dysplasias and carcinomas. Shahnavaz, S.A., Bradley, G., Regezi, J.A., Thakker, N., Gao, L., Hogg, D., Jordan, R.C. Cancer Res. (2001)
- Homozygous deletion of CDKN2A and codeletion of the methylthioadenosine phosphorylase gene in the majority of pleural mesotheliomas. Illei, P.B., Rusch, V.W., Zakowski, M.F., Ladanyi, M. Clin. Cancer Res. (2003)