Recent advances in the molecular genetics of malignant melanoma.
The study of the molecular basis for sporadic and inherited melanoma has rapidly moved forward over the past several years. The crucial observation that chromosome 9p21 abnormalities occurred with high frequency in sporadic melanomas, coupled with the molecular demonstration of common 9p21 LOH, led investigators to focus on this region. Examinations of patterns of inherited susceptibility to melanoma established 9p21 as the site of the MLM locus. The localization of the CDK inhibitor CDKN2 to the region enabled the demonstration of its alteration in numerous sporadic solid tumours. Most importantly, the gene has been implicated in the pathogenesis of both inherited and sporadic melanoma. Much work needs to be done to further our understanding of the prevalence of CDKN2 mutations and the prognoses they confer. In addition, continued avenues of investigation are likely to involve further application of this approach to other regions of genomic instability in melanoma, especially chromosomes 1, 6 and 10.
Haluska
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MIT Center for Cancer Research and Massachusetts General Hospital, Boston, MA 02114, USA.
Housman
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D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004198:Disease Susceptibility; D005190:Family; D016147:Genes, Tumor Suppressor; D008040:Genetic Linkage; D006801:Humans; D008545:Melanoma / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D012878:Skin Neoplasms / Q000235:genetics*
D002352:Carrier Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16