ALLELE LOSS ON CHROMOSOME 11Q AND MICROSATELLITE INSTABILITY IN MALIGNANT-MELANOMA

Loss of heterozygosity (allele loss, LOH) occurs frequently on the lon g arm of chromosome 11 in several types of cancer. We analysed 32 mela nomas (almost all metastatic lesions) for allele loss at eight loci al ong the length of chromosome 11 922-D11S899-D11S1324-D11S1313-D11S901- NCAM-D11S29- D11S968-qtel). The highest frequency of loss (38%) was at D11S29 (11q23.3). Of 13 melanomas which had lost an allele at one or more loci, all but one showed LOH at either D11S29 or NCAM (11q22). Th e region between these two loci is the most likely location of any tum our suppressor gene. Low frequencies of LOH occurred on 11p and there was little evidence for tumour suppressor loci outside the 11cen-q23.3 region. Unusually for melanomas, widespread microsatellite instabilit y, with slippage of several repeat units, was observed in two of 32 tu mours studied (and four other tumours showed new microsatellite allele s that differed by just one repeat unit from their normal counterparts ). However, no mutations of the mismatch repair genes hMSH2 and hMLH1 were detected in these two tumours, and the observed replication error s may result from mutations in other genes involved in mismatch repair or DNA replication. LOH on 11q and replication errors appear to compr ise part of the genetic pathways of several tumour types, including me lanomas. Copyright (C) 1996 Elsevier Science Ltd