BRCA1 Mutations in Primary Breast and Ovarian Carcinomas

Abstract

Loss of heterozygosity data from familial tumors suggest that BRCA1, a gene that confers susceptibility to ovarian and early-onset breast cancer, encodes a tumor suppressor. The BRCA1 region is also subject to allelic loss in sporadic breast and ovarian cancers, an indication that BRCA1 mutations may occur somatically in these tumors. The BRCA1 coding region was examined for mutations in primary breast and ovarian tumors that show allele loss at the BRCA1 locus. Mutations were detected in 3 of 32 breast and 1 of 12 ovarian carcinomas; all four mutations were germline alterations and occurred in early-onset cancers. These results suggest that mutation of BRCA1 may not be critical in the development of the majority of breast and ovarian cancers that arise in the absence of a mutant germline allele.

A targeted disruption of the murine Brca1 gene causes γ-irradiation hypersensitivity and genetic instability

“…These ®ndings directly illustrate the role of BRCA1 in maintaining the stability of the genome and provide some insights regarding the mechanism by which BRCA1 suppresses tumor formation. Notably, tumorigenesis in people with BRCA1 mutations occurs with relatively long latency and somatic mutations are rarely detected in sporadic cases (Easton, 1997;Futreal et al, 1994;Struewing et al, 1997;Xu and Solomon, 1996). In light of our ®ndings, we believe that this is primarily because the loss of BRCA1 does not directly promote tumorigenesis.…”

“…Our observation that the inactivation of p53 itself is not su cient to allow BRCA1 cells to proliferate but does cause formation of multiple proliferative foci suggests a involvement of multiple factors in the BRCA1 associated tumorigenesis. This may account for the relatively long latency of cancer incidence in people carrying Brca1 mutations and the rare incidence of somatic Brca1 mutations in sporadic cancers (Easton, 1997;Futreal et al, 1994;Struewing et al, 1997;Xu and Solomon, 1996).…”

BRCA1 5382insC mutation in sporadic and familial breast and ovarian carcinoma in Scotland

“…This implies that there has been a recombination event at the telomeric end of common ancestral haplotype in this family. Since the isolated case we identified carries the Icomplete' common haplotype, it is unlikely that she is closely related to the West Lothian family.Keywords: BRCA1; 5382insC; breast cancer; polymerase chain reaction The BRCAJ gene was first mapped to chromosome 17q by linkage analysis (Hall et al, 1990;Narod et al, 1991) and subsequently by positional cloning Futreal et al, 1994). The gene contains 22 coding exons distributed over more than 100 kb and codes for a protein of 1863 amino acids.…”

“…Keywords: BRCA1; 5382insC; breast cancer; polymerase chain reaction The BRCAJ gene was first mapped to chromosome 17q by linkage analysis (Hall et al, 1990;Narod et al, 1991) and subsequently by positional cloning Futreal et al, 1994). The gene contains 22 coding exons distributed over more than 100 kb and codes for a protein of 1863 amino acids.…”

A role for BRCA1 in sporadic breast cancer

“…BRCA1 germline mutations have been described in only a handful of sporadic breast cancer cases (Futreal et al, 1994;GarciaPatino et al, 1998) where they are likely to represent de novo mutations. No somatic BRCA1 gene mutations have been identified without simultaneous germline mutations, unlike ovarian cancer, where single somatic BRCA1-truncating mutations have been identified (Merajver et al, 1995).…”