Increased frequency of TP53 mutations in BRCA1 and BRCA2 ovarian tumours

We screened 81 ovarian tumours (30 BRCAI associated, 18 BRCA2 associated, a nd 33 sporadic) for somatic TP53 mutations using both DNA analysis and immu nostaining. TP53 mutations were significantly more frequent in tumours with mutations in BRCA1 (70% by immunostaining and 60% by DNA analysis) and BRC A2 (67% and 50%) compared to sporadic controls (39% and 30%) (P = 0.009). A higher proportion of tumours with BRCAI and BRCA2 mutations were poorly di fferentiated, and TP53 mutant tumours in all categories were also more like ly to be poorly differentiated. The poor differentiation of tumours with BR CAI and BRCA2 mutations may be directly related to the role of these genes in DNA repair, and the need to overcome cell cycle checkpoints, often throu gh loss of TP53. These results are consistent with the model of BRCA-induce d tumorigenesis in which loss of checkpoint control is necessary for tumour development. (C) 1999 Wiley-Liss, Inc.