title: Evaluation of the diagnostic accuracy of the stop codon (SC) assay for identifying protein-truncating mutations in the BRCA1and BRCA2genes in familial breast cancer.
abstract: Screening for protein-truncating mutations of the BRCA1 and BRCA2 genes is useful in genetic testing for familial breast cancer because, first, the methods are usually simple and not expensive, and second, the detected mutations indicate pathogenic mutations in general. We evaluated the diagnostic accuracy of the stop codon (SC) assay for detecting protein-truncating mutations in the BRCA1 and BRCA2 genes by comparing the results with DNA sequencing in samples from 29 patients with breast cancer from 24 Japanese families with a history of breast cancer. Protein-truncating mutations were detected in 5 of the 24 families (20.8%; two in the BRCA1 gene and three in the BRCA2 gene). Among the 176 DNA fragments examined using the SC assay, the existence of three protein-truncating mutations (one in the BRCA1 gene and two in the BRCA2gene) was predicted correctly by the assay. Only one reverse transcriptase-polymerase chain reaction fragment was positive for the SC assay but was negative using DNA sequencing. Our study showed clearly that the SC assay is sensitive (3 of 3, 100%) and specific (172 of 173, 99%) for detecting pathogenic protein-truncating mutations in the BRCA1 and BRCA2 genes, and that it could be useful for screening larger populations.
authors.affiliation: Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Sakayori
authors.forename: Masanori
authors.initials: M
authors.lastname: Kawahara
authors.forename: Kazuko
authors.initials: K
authors.lastname: Shiraishi
authors.forename: Tadashi
authors.initials: T
authors.lastname: Nomizu
authors.forename: Akira
authors.initials: A
authors.lastname: Shimada
authors.forename: Toshio
authors.initials: T
authors.lastname: Kudo
authors.forename: Rikiya
authors.initials: R
authors.lastname: Abe
authors.forename: Noriaki
authors.initials: N
authors.lastname: Ohuchi
authors.forename: Seiichi
authors.initials: S
authors.lastname: Takenoshita
authors.forename: Ryunosuke
authors.initials: R
authors.lastname: Kanamaru
authors.forename: Chikashi
authors.initials: C
authors.lastname: Ishioka
mesh_terms: D001681:Biological Assay; D001943:Breast Neoplasms / Q000209:etiology / Q000235:genetics*; D018388:Codon, Terminator; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D009154:Mutation; D017422:Sequence Analysis, DNA
chemical_list: D018388:Codon, Terminator