title: Double heterozygosity for mutations in the BRCA1 and BRCA2 genes in a breast cancer patient.
abstract: BACKGROUND
  Germline mutations in the tumor suppressor genes BRCA1 and BRCA2 confer substantial increased lifetime risk for breast cancer, and in the case of BRCA1, for ovarian carcinoma as well. These two genes alone account for the vast majority of hereditary breast cancer families. Numerous mutations have been described in each gene, the majority of which are small insertions or deletions resulting in expression of a truncated protein.
  
  
  METHODS
  Several common mutations can be detected using a polymerase chain reaction-mediated, site-directed mutagenesis assay, which transforms the amplicon derived from either the wild-type or mutant allele by adding or removing a restriction endonuclease site. We screened 49 putative sporadic breast tumors using this methodology, targeting four BRCA1 mutations (185delAG, 5382insC, R1443X, and E1250X) and a single BRCA2 mutation (6174delT).
  
  
  RESULTS
  Using the polymerase chain reaction-mediated, site-directed mutagenesis assay, we identified two mutations, namely, a 185delAG mutation (BRCA1) and a 6174delT mutation (BRCA2). Interestingly, these two mutations were found in the same sample. None of the remaining 48 breast tumors showed evidence of these mutations. Allele-specific oligonucleotide probes were then employed in conjunction with the Universal GeneComb Test Kit, which confirmed the presence of mutations.
  
  
  CONCLUSIONS
  Our data suggest that the common germline BRCA1 and BRCA2 mutations are infrequently encountered in sporadic breast cancers. The one case with dual BRCA1 and BRCA2 mutations suggests that this tumor may be hereditary in origin, despite the lack of a positive family history. Double heterozygosity for mutations in BRCA1 and BRCA2 may have increasingly significant implications with regard to predisposition to breast cancer.
authors.affiliation: Department of Pathology and Laboratory Medicine, Hartford Hospital, CT 06102, USA.
authors.forename: G J
authors.initials: GJ
authors.lastname: Tsongalis
authors.forename: D R
authors.initials: DR
authors.lastname: Linfert
authors.forename: R C
authors.initials: RC
authors.lastname: Johnson
authors.forename: R
authors.initials: R
authors.lastname: Ackroyd
authors.forename: M M
authors.initials: MM
authors.lastname: Berman
authors.forename: A
authors.initials: A
authors.lastname: Ricci
mesh_terms: D024682:BRCA2 Protein; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000473:pathology; D004273:DNA, Neoplasm / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D019398:Genes, BRCA1 / Q000235:genetics*; D005819:Genetic Markers; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D016297:Mutagenesis, Site-Directed; D009363:Neoplasm Proteins / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011933:Reagent Kits, Diagnostic; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D024682:BRCA2 Protein; D004273:DNA, Neoplasm; D005819:Genetic Markers; D009363:Neoplasm Proteins; D011933:Reagent Kits, Diagnostic; D014157:Transcription Factors