Preferential allelic expression can lead to reduced expression of BRCA1 in sporadic breast cancers.
BRCA1 is considered to be a tumor-suppressor gene, yet mutations in this gene are uncommon in sporadic breast tumors. We investigated whether mechanisms other than DNA mutations that affect the coding region might be involved in breast carcinogenesis. Since loss of expression of the BRCA1 gene would lead to lack of protein, we evaluated the level of BRCA1 mRNA in 21 normal epithelial specimens and in 74 breast carcinomas using quantitative reverse-transcription-polymerase-chain-reaction (RT-PCR). All normal breast epithelial samples expressed BRCA1 mRNA. On the other hand, the tumor specimens exhibited approximately 10-fold range of levels of BRCA1, with some specimens expressing barely detectable amounts of BRCA1 mRNA. The distribution in levels was significantly higher in normal breast epithelial cells than in tumor specimens (p = 0.004). Examination of the BRCA1 locus indicated that deletion of the BRCA1 gene may account for low levels of BRCA1 in a number of specimens. In addition, analysis of samples with relatively reduced levels of BRCA1 expression revealed preferential allele-specific expression in a number of cases, suggesting the presence of regulatory mutations. Our data suggest that the BRCA1 gene may be involved in sporadic breast carcinogenesis through a reduction in gene expression.
Ozçelik
H
H
Samuel Lunenfeld Research Institute, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Canada.
To
M D
MD
Couture
J
J
Bull
S B
SB
Andrulis
I L
IL
D000483:Alleles; D019313:BRCA1 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009154:Mutation
D019313:BRCA1 Protein