title: High proportion of missense mutations of the BRCA1 and BRCA2 genes in Japanese breast cancer families.
abstract: Mutations in either of two recently identified genes, BRCA1 and BRCA2, are thought to be responsible for approximately two-thirds of all cases of autosomal-dominantly inherited breast cancer. To examine the nature and frequency of BRCA1 and BRCA2 mutations in Japanese families exhibiting a high incidence of breast cancer, we screened 78 unrelated families in this category for mutations of these two genes. Examining the entire coding sequences as well as exon-intron boundaries of both genes by polymerase chain reaction (PCR) single-strand conformation polymorphism (SSCP) and multiplex-SSCP analysis, we identified possible disease-causing alterations in BRCA1 among affected members of 15 families and in BRCA2 in another 14 families. In 15 of those 29 families, the affected individuals carried missense mutations, although most germline mutations reported worldwide have been deletions or nonsense mutations. Our results, indicating that missense mutations of BRCA1 and BRCA2 tend to predominate over frameshifts or nonsense mutations in Japanese breast cancer families, will contribute significantly to an understanding of mammary tumorigenesis in Japan, and will be of vital importance for future genetic testing.
authors.affiliation: Department of Human Genome Analysis, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Katagiri
authors.forename: F
authors.initials: F
authors.lastname: Kasumi
authors.forename: M
authors.initials: M
authors.lastname: Yoshimoto
authors.forename: T
authors.initials: T
authors.lastname: Nomizu
authors.forename: K
authors.initials: K
authors.lastname: Asaishi
authors.forename: R
authors.initials: R
authors.lastname: Abe
authors.forename: A
authors.initials: A
authors.lastname: Tsuchiya
authors.forename: M
authors.initials: M
authors.lastname: Sugano
authors.forename: S
authors.initials: S
authors.lastname: Takai
authors.forename: M
authors.initials: M
authors.lastname: Yoneda
authors.forename: T
authors.initials: T
authors.lastname: Fukutomi
authors.forename: K
authors.initials: K
authors.lastname: Nanba
authors.forename: M
authors.initials: M
authors.lastname: Makita
authors.forename: H
authors.initials: H
authors.lastname: Okazaki
authors.forename: K
authors.initials: K
authors.lastname: Hirata
authors.forename: M
authors.initials: M
authors.lastname: Okazaki
authors.forename: Y
authors.initials: Y
authors.lastname: Furutsuma
authors.forename: Y
authors.initials: Y
authors.lastname: Morishita
authors.forename: Y
authors.initials: Y
authors.lastname: Iino
authors.forename: T
authors.initials: T
authors.lastname: Karino
authors.forename: H
authors.initials: H
authors.lastname: Ayabe
authors.forename: S
authors.initials: S
authors.lastname: Hara
authors.forename: T
authors.initials: T
authors.lastname: Kajiwara
authors.forename: S
authors.initials: S
authors.lastname: Houga
authors.forename: Y
authors.initials: Y
authors.lastname: Miki
mesh_terms: D024682:BRCA2 Protein; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D019398:Genes, BRCA1; D006801:Humans; D007564:Japan; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D014157:Transcription Factors / Q000235:genetics
chemical_list: D024682:BRCA2 Protein; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D014157:Transcription Factors