LOSS OF HETEROZYGOSITY AT 11Q23.1 IN BREAST CARCINOMAS - INDICATION FOR INVOLVEMENT OF A GENE DISTAL AND CLOSE TO ATM

Previous reports have suggested that heterozygotes for ataxia-telangie ctasia (A-T) have an increased risk of cancer, in particular breast ca ncer. The ATM gene, responsible for A-T, was recently cloned. Loss of heterozygosity (LOH) in the chromosome band 11q23, where the ATM gene is located, has been reported in several types of tumours including br east carcinomas. Whether the ATM gene is the target, and the sole targ et, for the LOH seen in this region is not yet known. In this study, 1 69 primary breast carcinomas and 10 metastases were examined for allel ic imbalance (AI) using 10 microsatellite markers mapping to 11q23.1. Nine of the markers reside within a 10 Mb region surrounding the ATM g ene, whereas the tenth locus, APOC-3, is located more than 12 Mb telom eric from this region. The highest frequencies of alteration were foun d for APOC-3 (45%), and for two markers located approximately 200 and 900 kb telomeric from ATM, D11S1294 (44%) and D11S1818 (44%). The mark er located within the ATM gene, D11S2179, was altered in 37% of the in formative tumours. The present deletion map indicates that three disti nct regions at 11q23.1 may be involved in breast cancer development; o ne between the markers DIlS1294 and D11S1818, a second close to APOC-3 , and a third that is possibly the ATM-gene itself. (C) 1997 Wiley-Lis s, Inc.