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Increased frequency of TP53 mutations in BRCA1 and BRCA2 ovarian tumours
Author(s) -
Ramus Susan J.,
Bobrow Lynda G.,
Pharoah Paul D.P.,
Finnigan Damon S.,
Fishman Ami,
Altaras Marco,
Harrington Patricia A.,
Gayther Simon A.,
Ponder Bruce A.J.,
Friedman Lori S.
Publication year - 1999
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/(sici)1098-2264(199906)25:2<91::aid-gcc3>3.0.co;2-5
Subject(s) - biology , immunostaining , carcinogenesis , cancer research , somatic cell , ovarian cancer , mutation , germline mutation , gene , brca2 protein , dna repair , cell cycle , tumor suppressor gene , cancer , genetics , immunohistochemistry , immunology
Abstract We screened 81 ovarian tumours (30 BRCA1 associated, 18 BRCA2 associated, and 33 sporadic) for somatic TP53 mutations using both DNA analysis and immunostaining. TP53 mutations were significantly more frequent in tumours with mutations in BRCA1 (70% by immunostaining and 60% by DNA analysis) and BRCA2 (67% and 50%) compared to sporadic controls (39% and 30%) ( P = 0.009). A higher proportion of tumours with BRCA1 and BRCA2 mutations were poorly differentiated, and TP53 mutant tumours in all categories were also more likely to be poorly differentiated. The poor differentiation of tumours with BRCA1 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 through loss of TP53 . These results are consistent with the model of BRCA ‐induced tumorigenesis in which loss of checkpoint control is necessary for tumour development. Genes Chromosom. Cancer 25:91–96, 1999. © 1999 Wiley‐Liss, Inc.