WIDESPREAD MICROSATELLITE INSTABILITY IN SEBACEOUS TUMORS OF PATIENTSWITH THE MUIR-TORRE-SYNDROME

Muir-Torre syndrome (MTS) is an autosomal dominant disorder characteri zed by the presence of at least one sebaceous gland tumour and a minim um of one visceral malignant tumour, Recently microsatellite instabili ty (MSI) has been detected in the tumours of patients with MTS and ger mline mutations of the hMSH2 and hMLH1 mismatch repair genes have been detected in some patients with this syndrome, To determine if the tum ours of patients with MTS hare widespread genomic instability and whet her loss of heterozygosity (LOH) in the chromosomal regions containing hMSH2 and hMLH1 is detectable, MSI and LOH were examined at 10 dinucl eotide repeats on chromosomes 2p, 3p, 5q, 9p, 17p and 18q. Data were o btained from six sebaceous gland tumours and two adenocarcinomas of th e colon from three patients of two Muir-Torre families, MSI was detect ed at more than half of the loci tested in all sebaceous tumours exami ned. In addition, there was LOH at D2S119 in one sebaceoma and one seb aceous carcinoma from one patient, The colon carcinomas from two patie nts showed MSI at five of the 10 loci analysed, These results show tha t widespread MSI is a feature of tumours in patients with MTS. In addi tion, the finding of LOH at D2S119, a marker located in the vicinity o f hMSH2, in sebaceous tumours of one patient indicates that this gene may have a pathogenetic role in this patient.