LOSS OF HETEROZYGOSITY IN HUMAN BREAST CARCINOMAS IN THE ATAXIA-TELANGIECTASIA, COWDEN DISEASE AND BRCA1 GENE REGIONS

To appreciate the involvement of known or potential susceptibility gen es in sporadic breast tumors, we have searched for chromosomal deletio ns by studying loss of heterozygosity (LOH) at 43 microsatellite (CA)( n) markers from human chromosomes 10, 11 and 17, in 115 unselected con secutive samples of breast carcinoma with particular emphasis on speci fic regions. No site of consistent LOH was identified on chromosome 10 . Five regions of LOH were contained within bands q22-24 of chromosome 11 for which nearly 50% of the tumors had LOH at at least one marker. This region is thus a major site of deletion in breast cancer and sev eral tumor suppressor genes seem to be involved. One of them may be th e ataxia telangiectasia (ATM) gene which is located in one of the affe cted regions. Five regions of LOH, one of which is within the BRCA1 ge ne area, were recognized along chromosome 17. LOH at three of these re gions were found in highly proliferative tumors, When combined with a previous study of chromosome 13 with emphasis on BRCA2 and Rb1 genes, this work allowed to distinguish a total of 12 regions of LOH, variabl y affected in breast tumors and correlated with prognostic parameters.