Characterization of the neoplastic phenotype in the familial atypical multiple-mole melanoma-pancreatic carcinoma syndrome

Abstract

Background: Previous studies suggest that the familial atypical multiple-mole melanoma (FAMMM) syndrome may predispose affected families to nonmelanoma carcinomas, including adenocarcinoma of the pancreas. It has been found that many of these families harbor mutations in the CDKN2A gene on chromosome 9p21. The phenotypic expression of CDKN2A mutations in these families has not been characterized fully.

Methods: The authors studied eight families that appeared to inherit multiple nevi, cutaneous melanomas, and pancreatic carcinomas in association with a CDKN2A germline mutation. The expression of disease within these families was examined, and segregation ratios were estimated to assess the patterns of inheritance according to various definitions of phenotype.

Results: Either multiple nevi or pancreatic carcinoma was diagnosed in 53% of first-degree relatives of the probands. The offspring of parents affected with multiple nevi, melanoma, or pancreatic carcinoma were significantly more likely to be affected themselves compared with the offspring of unaffected parents (48.9% vs. 16.7%; P = 0.004).

Conclusions: The current results provide additional evidence that multiple nevi, melanoma, or pancreatic carcinoma may be inherited as autosomal-dominant traits in families known to harbor CDKN2A mutations. Other malignancies may be a part of the phenotype in these families, although this hypothesis requires additional study.