1. Frequent loss of BRCA1 mRNA and protein expression in sporadic ovarian cancers.
- Author
-
Russell PA, Pharoah PD, De Foy K, Ramus SJ, Symmonds I, Wilson A, Scott I, Ponder BA, and Gayther SA
- Subjects
- BRCA1 Protein biosynthesis, DNA Mutational Analysis, DNA, Neoplasm genetics, Female, Heteroduplex Analysis, Humans, Neoplasm Proteins biosynthesis, Neoplasm Proteins genetics, Ovarian Neoplasms metabolism, Ovarian Neoplasms pathology, Polymorphism, Single-Stranded Conformational, BRCA1 Protein deficiency, Gene Deletion, Genes, BRCA1, Loss of Heterozygosity, Mutation, Neoplasm Proteins deficiency, Ovarian Neoplasms genetics, RNA, Messenger genetics, RNA, Neoplasm genetics
- Abstract
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., (Copyright 2000 Wiley-Liss, Inc.)
- Published
- 2000
- Full Text
- View/download PDF