Encyclopedia of Cancer

Living Edition
| Editors: Manfred Schwab


  • Mark Harland
Living reference work entry
DOI: https://doi.org/10.1007/978-3-642-27841-9_966-2



Cyclin-dependent kinase inhibitor 2A gene (CDKN2A), the first identified melanoma predisposition gene, encodes the tumor suppressor proteins p16 and ARF.


Identification of CDKN2A

The 9p21-22 chromosomal region was originally implicated in the development of melanomas through a combination of cytogenetic and loss of heterozygosity (LOH) studies. Subsequent linkage analysis in melanoma families indicated that this region harbored a melanoma predisposition locus. Homozygous deletions in cell lines derived from several different tumor types narrowed down the region significantly. This led to the isolation, by two independent groups, of the cell cycle regulatory gene encoding the cyclin-dependent kinase (CDK) inhibitor, p16, which had been previously identified in a yeast two-hybrid screen to identify proteins that bound to CDK4 (Fig. 1).


Melanoma Risk Inhibit Cell Cycle Progression CDKN2A Gene Multiple Primary Tumor Alternative Reading Frame 
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  1. Bishop JN, Harland M, Randerson-Moor J et al (2007) Management of familial melanoma. Lancet Oncol 8(1):46–54CrossRefPubMedGoogle Scholar
  2. Goldstein AM, Chan M, Harland M et al (2007) Features associated with germline CDKN2A mutations: a GenoMEL study of melanoma-prone families from three continents. J Med Genet 44(2):99–106CrossRefPubMedGoogle Scholar
  3. Hayward NK (2003) Genetics of melanoma predisposition. Oncogene 22(20):3053–3056CrossRefPubMedGoogle Scholar
  4. Sharpless NE (2005) INK4a/ARF: a multifunctional tumor suppressor locus. Mutat Res 576(1–2):22–38CrossRefPubMedGoogle Scholar
  5. Sharpless E, Chin L (2003) The INK4a/ARF locus and melanoma. Oncogene 22(20):3092–3098CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.Section of Epidemiology and Biostatistics, Cancer Research UK Clinical CentreLeeds Institute of Molecular Medicine, St. James’s University HospitalLeedsUK