NEVOID BASAL-CELL CARCINOMA SYNDROME

The nevoid basal cell carcinoma syndrome is an autosomal dominant diso rder that predisposes to basal cell carcinomas ofthe skin, ovarian fib romas, and medulloblastomas. Unlike other hereditary disorders associa ted with cancer, it features widespread developmental defects. Laborat ory studies of radiation sensitivity and chromosome instability over t he past 20 years have generally yielded negative or inconclusive resul ts. Recently, screening for allelic loss in sporadic and hereditary ba sal cell carcinomas, hereditary ovarian fibromas, and sporadic medullo blastomas provided evidence for a tumor suppressor gene on chromosome 9q, important in all three tumor types. Demonstration of a chromosome 9q deletion in an unusual patient with this syndrome and genetic linka ge studies in large kindreds indicated that the nevoid basal cell carc inoma syndrome gene maps to the exact same location lost in tumors. Th ese data show that tumors arise with homozygous inactivation of the ge ne and imply that it normally functions as a tumor suppressor. In cont rast, hemizygous germ-line mutations lead to multiple congenital anoma lies.