Chromosome rearrangements in dysplastic nevus syndrome predisposing to malignant melanoma

The dysplastic nevus syndrome (DNS) is an autosomal dominant trait characterized by multiple atypical skin moles and a propensity to malignant melanoma. We studied chromosomes from a three-generation DNS family in 1977. Cells cultured from normal skin and dysplastic nevi showed an elevation in chromosome rearrangements with nonrandom breakpoints and clonal proliferation marked by chromosome change. The DNS qualifies as a chromosome instability disorder, the first known to manifest dominant inheritance and a clear discernible premalignant state. The DNS road to malignancy may logically proceed by genomic alterations including translocations, duplications, and deletions.