Dysplastic nevus syndrome: ultraviolet hypermutability confirmed in vitro by elevated sister chromatid exchanges

The dysplastic nevus syndrome (DNS) is a clinical and genetic entity in which affected individuals have increased numbers of dysplastic nevi and a markedly increased risk of developing one or more cutaneous melanomas. Sister chromatid exchanges (SCE) are one of the cytogenetic end points that are positively correlated with the mutation rate and may therefore be used to estimate the spontaneous and the UV-induced mutagenesis in cultured and stored fibroblasts. SCE were presented and stained according to the Hoechst-Giemsa method. The normal control fibroblasts showed 9.48 +/- 1.74 SCE per metaphase (n = 23) with an UV-C-induced increase (delta SCE) of 1.61 +/- 0.53 SCE per mJ/cm2 in the range of 0-5 mJ/cm2. Fibroblasts from DNS patients with melanoma (n = 12) showed normal values of spontaneous SCE but a significant increase (p = 0.01) of 2.43 +/- 0.68 SCE per mJ/cm2. As in xeroderma pigmentosum, UV-C-induced delta SCE appears as a valuable tool for measuring the individual hypermutability in DNS. delta SCE indicates the increased susceptibility to UV-induced somatic mutations and may be etiologically related to the increased melanoma incidence in DNS.