INHERITED SUSCEPTIBILITY TO SEVERAL CANCERS BUT ABSENCE OF LINKAGE BETWEEN DYSPLASTIC NEVUS SYNDROME AND CDKN2A IN A MELANOMA FAMILY WITH AMUTATION IN THE CDKN2A (P16INK4A) GENE

Genetic predisposition plays an important role in the development of n early 10% of cases of cutaneous malignant melanoma (CMM). The CDKN2A g ene has been described as responsible for melanoma susceptibility in a proportion of families with CMM linked to 9p. CDKN2A encodes a cyclin -dependent kinase inhibitor also implicated in the carcinogenesis of s everal sporadic tumors. Even though the incidence of other cancers is higher in CMM families, pancreatic adenocarcinoma is the only other we ll demonstrated cancer associated with CDKN2A mutations in some CMM pe digrees. We describe a family with four cases of CMM, eight patients a ffected by other cancers, and nine patients affected by dysplastic nev us (DN) syndrome. A CDKN2A frameshift mutation (358delG) was present i n all the CMM patients, in at least three of the patients with other c ancers (CDKN2A status is unknown in four patients), and in only two of the DN patients (CDKN2A status is unknown in one patient). An absence of linkage between chromosome 9p markers and the 358delG CDKN2A mutat ion and DN was detected, indicating genetic heterogeneity for DN and C MM in this family. The study strongly suggests that CDKN2A mutations a re involved not only in the predisposition to CMM but also to several other types of cancer.