Cyclin-dependent kinase inhibitor 2A gene (CDKN2A), the first identified melanoma predisposition gene, encodes the tumor suppressor proteins p16 and ARF.
Characteristics
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).
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References
1.
Bishop JN, Harland M, Randerson-Moor J et al. (2007) Management of familial melanoma. Lancet Oncol 8(1):46–54PubMedCrossRefGoogle 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):99–106PubMedCrossRefGoogle Scholar
1.Section of Epidemiology and BiostatisticsCancer Research UK Clinical Centre, Leeds Institute of Molecular Medicine, St. James's University HospitalLeedsUK