ALLELIC LOSS AT BRCA1, BRCA2, AND ADJACENT LOCI IN RELATION TO TP53 ABNORMALITY IN BREAST-CANCER

Cells with abnormal TP53 lose cell cycle checkpoints, resulting in gen omic instability and neoplastic transformation. However, the evidence linking the tumor-specific targets of genomic alteration to an abnorma l TP53 is limited. The present study tested the hypothesis that TP53 a bnormalities are correlated with an increased frequency of deletion of breast cancer susceptibility loci (17q and 13q) in breast carcinomas. Tumors from 90 patients were examined for TP53 abnormality and loss o f heterozygosity (LOH) at 11 loci on 17q (17q11.2-21) and 13q (13q12-1 4), including the loci for BRCA1 and BRCA2. A higher frequency of LOH was consistently found at 17q or 13q loci in tumors with an abnormal T P53. The increased LOH in relation to TP53 abnormality was statistical ly significant at the BRCA1, D17S588, and D13S267 loci (P < 0.05) but not at the locus for BRCA2 (P = 0.64). These observations imply a poss ible link between an abnormal TP53 and specific genomic deletions of b reast cancer susceptibility loci, which may provide clues to the role of TP53 during breast tumorigenesis. (C) 1997 Wiley-Liss, Inc.