Frequent loss of BRCA1 mRNA and protein expression in sporadic ovarian cancers.
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.
Russell
P A
PA
CRC Department of Oncology, Strangeways Research Laboratory, Cambridge, UK. paul.russell@srl.cam.ac.uk
Pharoah
P D
PD
De Foy
K
K
Ramus
S J
SJ
Symmonds
I
I
Wilson
A
A
Scott
I
I
Ponder
B A
BA
Gayther
S A
SA
D019313:BRCA1 Protein / Q000096:biosynthesis / Q000172:deficiency*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D019398:Genes, BRCA1; D020180:Heteroduplex Analysis; D006801:Humans; D019656:Loss of Heterozygosity; D009154:Mutation; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018807:Polymorphism, Single-Stranded Conformational; D012333:RNA, Messenger / Q000235:genetics*; D012334:RNA, Neoplasm / Q000235:genetics*
D019313:BRCA1 Protein; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm