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Mutations in the BRCA1 gene in Japanese breast cancer patients
Author(s) -
Katagiri Toyomasa,
Emi Mitsuru,
Ito Isao,
Kobayashi Kanji,
Yoshimoto Masataka,
Iwase Takuji,
Kasumi Fujio,
Miki Yoshio,
Skolnick Mark H.,
Nakamura Yusuke
Publication year - 1996
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/(sici)1098-1004(1996)7:4<334::aid-humu7>3.0.co;2-8
Subject(s) - missense mutation , biology , nonsense mutation , genetics , single strand conformation polymorphism , breast cancer , exon , germline mutation , stop codon , carcinogenesis , mutation , gene , germline , cancer research , cancer
Predisposing germline mutations in the BRCA1 gene were identified recently in families with 17q‐linked breast and ovarian cancers. Using single‐strand conformation polymorphism (SSCP) analysis, we examined primary breast cancers for mutations in coding exons of BRCA1 in a panel of 103 patients, of whom all either represented early‐onset cases (< 35 of age), were members of multiply‐affected families, and/or had developed bilateral breast cancers. Mutations were detected in tumors from four patients, all of whom had developed breast cancers bilaterally: a frame‐shift due to a 2‐bp deletion at codon 797; a nonsense mutation at codon 1214; and two missense mutations, one at codon 271 leading to Val → Met substitution, and the other at codon 1150 leading to Pro → Ser substitution. In each case the same mutation was present in constitutional DNA. The mean age of onset was 49 years among the Japanese carriers of BRCA1 mutations identified in this study, in contrast to the mean age of 35 observed among carriers of BRCA1 mutations in a similar U.S. study (Futreal et al., 1994). The evidence reported here supports a rather limited role of BRCA1 in breast carcinogenesis. © 1996 Wiley‐Liss, Inc.