title: Identification and evaluation of 55 genetic variations in the BRCA1 and the BRCA2 genes of patients from 50 Japanese breast cancer families.
abstract: We sequenced approximately 23 kb genomic regions containing all the coding exons and their franking introns of two breast cancer susceptibility genes, BRCA1 and BRCA2, of 55 individuals from 50 unrelated Japanese breast cancer families. We identified 55 single-nucleotide polymorphisms (SNPs) (21 in BRCA1 and 34 in BRCA2) containing nine pathogenic protein-truncating mutations (four in BRCA1 and five in BRCA2 from ten patients). Among the remaining 46 SNPs, allele frequencies of 40 were examined in both the breast cancer patients and 28 healthy volunteers with no breast cancer family history by PCR-RFLP or by direct DNA sequencing. Twenty-eight SNPs were common and were also found in the healthy volunteers and/or a SNP database. The remaining 18 were rare (allele frequency <0.05) and were not found in the healthy volunteers and/or the database. The pathogenic significance of these coding SNPs (cSNPs) remains to be clarified. The SNP information from this study will be useful in the future genetic testing of both BRCA1 and BRCA2 genes in the Japanese population.
authors.affiliation: Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.|Department of Second Surgery, Fukushima Prefecture College School of Medicine, Fukushima, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Kawahara
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.affiliation: Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.|Division of Surgical Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Shiraishi
authors.affiliation: Department of Surgery, Hoshi General Hospital, Koriyama, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Nomizu
authors.affiliation: Division of Surgical Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Takeda
authors.affiliation: Tohoku Familial Tumor Association, Koriyama, Japan.
authors.forename: Rikiya
authors.initials: R
authors.lastname: Abe
authors.affiliation: Division of Surgical Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Ohuchi
authors.affiliation: Department of Second Surgery, Fukushima Prefecture College School of Medicine, Fukushima, Japan.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Takenoshita
authors.affiliation: Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan. chikashi@idac.tohoku.ac.jp.
authors.forename: Chikashi
authors.initials: C
authors.lastname: Ishioka
mesh_terms: D000483:Alleles; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D019992:Databases as Topic; D005091:Exons; D005192:Family Health; D005787:Gene Frequency; D019398:Genes, BRCA1; D014644:Genetic Variation; D006801:Humans; D007438:Introns; D007564:Japan; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA
chemical_list: D024682:BRCA2 Protein