LOSS OF HETEROZYGOSITY IN SPORADIC BREAST-TUMORS AT THE BRCA2 LOCUS ON CHROMOSOME 13Q12-Q13

Loss of heterozygosity (LOH) on chromosome 13 occurs on 25-30% of brea st tumours. This may reflect the inactivation of the retinoblastoma su sceptibility gene RBI. However, recently another candidate tumour-supp ressor gene has been identified on chromosome 13 by linkage analysis, the breast cancer susceptibility gene BRCA2. To investigate the involv ement of BRCA2 in sporadic breast cancer 200 breast tumours were teste d for LOH on chromosome band 13q12-q14, using 11 highly polymorphic mi crosatellite markers. LOH was found in 65 tumours, which all showed si multaneously loss of BRCA2 and RB1. Of 12 breast tumour cell Lines tes ted with polymorphic microsatellite markers, seven showed a contiguous region of homozygosity on 13q12-q14, suggesting LOH in the tumour fro m which the cell line had been derived. One cell line showed homozygos ity in the BRCA2 region and heterozygosity at RBI. This is the only in dication that BRCA2 is a distinct target for LOH on chromosome 13 in a ddition to RB1.