Age does not appear to be a major indicator of CDKN2A or CDK4 mutations in melanoma patients in Spain.

Cutaneous malignant melanoma is a potentially fatal formof skin cancer whose aetiology is heterogeneous andcomplex. Genetic factors and environmental carcinogensare believed to contribute to its development. Approxi-mately 5–12% of all cases of melanoma arise in a familialcontext [1]. Familial cutaneous melanoma cases fre-quently present an earlier onset than sporadic cutaneousmelanoma [2].The pattern of heredity in familial melanoma isconsistent with an autosomal dominant inheritance withincomplete penetrance [3]. Familial melanoma is asso-ciated with germline mutations in CDKN2A/ARF on 9p21and, to a lesser extent, in CDK4 on 12q13. Variableproportions of germline mutations in CDKN2A have beenidentified in melanoma kindreds [4–10]. The median ageat diagnosis in patients belonging to families carryinggermline CDKN2A mutations is significantly lower than inpatients belonging to families without mutations. In somepreviously reported studies [11–14], a low prevalence ofgermline CDKN2A mutations was found in patientsdiagnosed with melanoma in the under 40-year (USA),25-year (France) or 20-year (Sweden, Australia) agegroups in fair-skinned populations. As the CDKN2Amutation penetrance varies with the melanoma popula-tion incidence rates [15], it is of interest to determinewhat occurs in darker skinned populations with a lowermelanoma incidence [16]. The aim of this study was toinvestigate the presence of germline CDKN2A mutationsin patients with early-onset melanoma in the Spanishpopulation.