CDKN2A mutations in Spanish cutaneous malignant melanoma families and patients with multiple melanomas and other neoplasia

The CDKN2A gene has been implicated in cutaneous malignant melanoma (CMM) i n about 40% of families with linkage to chromosome 9p21, while a small prop ortion of families have mutations in the CDK4 gene. In order to estimate th e importance of these genes in the predisposition to CMM in Spanish familie s and patients we have analysed, by SSCA, a total of 56 subjects belonging to 34 CMM families, and nine patients with multiple CMM and other neoplasia . We have detected germline CDKN2A mutations in six out of the 34 families (17%). A frameshift mutation (358delG) and four missense mutations (G59V, G 101W (two cases), D84Y, and R87W) were identified. Five CMM patients from d ifferent families (14%) carried the A148T variant, which is known not to af fect p16 activity. No mutations were detected in the patients with multiple CMM or other neoplasms. We have not found mutations either in exon 1 beta of the CDKN2A gene or in exon 2A of CDK4. Linkage analysis of the 9p21 regi on showed exclusion for one of the families for CMM and for four families f or CMM/dysplastic naevi. This study indicates a small role for CDKN2A in Sp anish CMM families and suggests that other genes are also responsible for C MM predisposition.