Loss of heterozygosity in sporadic breast tumours at the BRCA2 locus on chromosome 13q12-q13.

Loss of heterozygosity (LOH) on chromosome 13 occurs on 25-30% of breast tumours. This may reflect the inactivation of the retinoblastoma susceptibility gene RB1. However, recently another candidate tumour-suppressor gene has been identified on chromosome 13 by linkage analysis, the breast cancer susceptibility gene BRCA2. To investigate the involvement of BRCA2 in sporadic breast cancer 200 breast tumours were tested for LOH on chromosome band 13q12-q14, using 11 highly polymorphic microsatellite markers. LOH was found in 65 tumours, which all showed simultaneously loss of BRCA2 and RB1. Of 12 breast tumour cell lines tested with polymorphic microsatellite markers, seven showed a contiguous region of homozygosity on 13q12-q14, suggesting LOH in the tumour from which the cell line had been derived. One cell line showed homozygosity in the BRCA2 region and heterozygosity at RB1. This is the only indication that BRCA2 is a distinct target for LOH on chromosome 13 in addition to RB1.