Detection of microsatellite alterations in the spectrum of melanocytic nevi in patients with or without individual or family history of melanoma.

We studied a group of patients with or without individual or family history of melanoma for the occurrence of genetic alterations at microsatellite DNA sequences, usually referred to as microsatellite instability (MSI), and loss of heterozygosity (LOH). Microsatellite analysis of 3 markers located on chromosome 9p21-22 was performed for 88 melanocytic lesions, including 27 melanomas and 35 dysplastic and 26 common nevi, from 48 patients. Three additional markers, on 11q23, 17q21 and 5q22, were investigated in 16 melanomas. Overall, microsatellite alterations of the type usually considered low-level instability at 9p21-22 were observed in 22% of melanomas and 31% of dysplastic and 23% of common nevi. LOH at the same loci was found in 15% of melanomas and 8% of dysplastic nevi but never in common nevi. Cases with a positive family history of melanoma compared to those with a negative family history showed a higher microsatellite alteration frequency (43% vs. 20%), and the same was observed in melanoma compared to non-melanoma carriers (31% vs. 16%). Our results show that (i) MSI is common in all melanocytic lesions, though with differences in the group of patients which could have clinical relevance if confirmed, whereas LOH is restricted to melanomas and dysplastic nevi; (ii) various melanocytic lesions from the same patient represent clonally distinct tumors; (iii) the phenotype suggestive of DNA repair deficiency is influenced by a family or an individual history of melanoma; (iv) the microsatellite alteration frequency correlates with patient groups ordered according to increasing melanoma risk. Copyright 2000 Wiley-Liss, Inc.