Frequent loss of BRCA1 mRNA and protein expression in sporadic ovarian cancers

Germline mutations in the BRCAI gene cause inherited susceptibility to brea st and ovarian cancers. However, somatic mutations of BRCAI are rare in spo radic breast and ovarian tumours. To establish whether BRCAI is altered dur ing the development of sporadic ovarian cancer by mechanisms other than som atic mutation, we have analysed 57 sporadic epithelial ovarian tumours for BRCAI 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 mutati ons of BRCAI and LOH at the BRCAI locus were detected in 3.5% and 44% of in formative tumours, respectively; there was no significant correlation betwe en the levels of protein and RNA expression and the DNA mutation and/or LOH status. Together, these data suggest that expression of BRCAI is down-regu lated at the level of transcription during the development of sporadic ovar ian cancers. Int. J. Cancer 87:317-321, 2000. (C) 2000 Wiley-Liss, Inc.