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 DN A sequences, usually referred to as microsatellite instability (MSI), and l oss of heterozygosity (LOH). Microsatellite analysis of 3 markers located o n chromosome 9p21-22 was performed for 88 melanocytic lesions, including 27 melanomas and 35 dysplastic and 26 common nevi, from 48 patients. Three ad ditional markers, on 11q23, 17q21 and 5q22, were investigated in 16 melanom as, Overall, microsatellite alterations of the type usually considered low- level instability at 9p21-22 were observed in 22% of melanomas and 31% of d ysplastic 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 famil y 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 le sions, though with differences in the group of patients which could have cl inical relevance if confirmed, whereas LOH is restricted to melanomas and d ysplastic nevi; (ii) various melanocytic lesions from the same patient repr esent clonally distinct tumors; (iii) the phenotype suggestive of DNA repai r deficiency is influenced by a family or an individual history of melanoma ; (iv) the microsatellite alteration frequency correlates with patient grou ps ordered according to increasing melanoma risk. Int. J, Cancer 86: 255-26 1, 2000, (C) 2000 Wiley-Liss, Inc.