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Frequent loss of BRCA1 mRNA and protein expression in sporadic ovarian cancers
Author(s) -
Russell Paul A.,
Pharoah Paul D.P.,
De Foy Karen,
Ramus Susan J.,
Symmonds Ian,
Wilson Annie,
Scott Ian,
Ponder Bruce A.J.,
Gayther Simon A.
Publication year - 2000
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/1097-0215(20000801)87:3<317::aid-ijc2>3.0.co;2-b
Subject(s) - germline mutation , biology , somatic cell , ovarian cancer , germline , cancer research , messenger rna , gene , brca2 protein , rna , gene expression , mutation , cancer , genetics
Germline mutations in the BRCA1 gene cause inherited susceptibility to breast and ovarian cancers. However, somatic mutations of BRCA1 are rare in sporadic breast and ovarian tumours. To establish whether BRCA1 is altered during the development of sporadic ovarian cancer by mechanisms other than somatic mutation, we have analysed 57 sporadic epithelial ovarian tumours for BRCA1 protein and RNA expression. Reduced or absent protein expression was observed in 90% of tumours. Decreased protein expression was significantly associated with a reduction in the levels of RNA expression. Somatic mutations of BRCA1 and LOH at the BRCA1 locus were detected in 3.5% and 44% of informative tumours, respectively; there was no significant correlation between the levels of protein and RNA expression and the DNA mutation and/or LOH status. Together, these data suggest that expression of BRCA1 is down‐regulated at the level of transcription during the development of sporadic ovarian cancers. Int. J. Cancer 87:317–321, 2000. © 2000 Wiley‐Liss, Inc.