Analysis of the CDKN2A and CDK4 genes and HLA-DR and HLA-DQ alleles in twoSpanish familial melanoma kindreds

Some confusion exists in the literature about which criteria should be used to define familial melanoma, This could explain the different reported fre quencies of mutations in predisposing genes, mostly CDKN2A, in these patien ts. This study evaluated the human leucocyte antigen (HLA) class II genotyp e and the presence of mutations in CDKN2A and CDK4 genes in 2 families with very different clinical features. The family with a germinal mutation in e xon 2 of CDKN2A (Gly(101)Try) presented the following clinical features: 3 first-degree affected members, I of whom had 2 melanomas, and all the melan omas appearing before 35 years of age. In contrast, the second family did n ot present any mutation in the studied genes and included 2 first-degree af fected members diagnosed at over 45 years of age. Neither family showed an association with HLA genotype, Other genes are also involved in familial me lanoma but, when the CDKN2A gene is affected, some clinical features seem t o be uniform.