Genetics in melanoma.
Melanoma is the leading cause of death from skin tumors worldwide, with an annual increase in incidence over the past decade. The molecular mechanisms involved in melanoma pathogenesis are beginning to be unraveled. While a family history of melanoma and exposure to ultraviolet irradiation have been known for years as risk factors in melanoma development, the precise genes involved in inherited predisposition were defined only in the past decade. Germline mutations in two genes that play a pivotal role in controlling cell cycle and division--CDKN2A and cyclin-dependent kinase 4 (CDK4)--have been detected in autosomal, dominant, high penetrance familial melanoma cases. In addition to these two highly penetrant genes, germline mutations and polymorphisms in a few low penetrance genes have been reported in familial melanoma cases: melanocortin-1 receptor, epidermal growth factor, glutathione s-transferase M1, cytochrome p450 debrisoquine hydroxylase locus (CYP2D6) and vitamin D receptor.
Stahl
Shy
S
Department of Plastic and Reconstructive Surgery, Sheba Medical Center, Tel Hashomer, Israel.
Bar-Meir
Eran
E
Friedman
Eitan
E
Regev
Eli
E
Orenstein
Arie
A
Winkler
Eyal
E
D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D004815:Epidermal Growth Factor / Q000235:genetics; D019942:Genes, p16; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008545:Melanoma / Q000235:genetics*; D019683:Penetrance; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics; D018167:Receptors, Calcitriol / Q000235:genetics
D019389:Cytochrome P-450 CYP2D6; D004815:Epidermal Growth Factor; D005982:Glutathione Transferase; D044102:Receptor, Melanocortin, Type 1; D018167:Receptors, Calcitriol