title: Detection of BRCA1 and BRCA2 germline mutations in Japanese population using next-generation sequencing.
abstract: Tumor suppressor genes BRCA1 and BRCA2 are the two main breast and ovarian cancer susceptibility genes, and their genetic testing has been used to evaluate the risk of hereditary breast and ovarian cancer (HBOC). While several studies have reported the prevalence of BRCA1 and BRCA2 mutations in Japanese populations, there is insufficient information about deleterious mutations compared with western countries. Moreover, because many rare variants are found in BRCA1 and BRCA2, both of which encode large proteins, it is difficult to sequence all coding regions using the Sanger method for mutation detection. In this study, therefore, we performed next-generation sequencing (NGS) analysis of the entire coding regions of BRCA1 and BRCA2 in 135 breast and/or ovarian cancer patients. Deleterious BRCA1 and BRCA2 mutations were detected in 10 patients (7.4%) by NGS analysis. Of these, one mutation in BRCA1 and two in BRCA2 had not been reported previously. Furthermore, a BRCA2 mutation found in a proband was also identified in two unaffected relatives. These data suggest the utility of screening BRCA1 and BRCA2 mutations by NGS in clinical diagnosis.
authors: Genome Analysis Center, Yamanashi Prefectural Central Hospital Kofu, Japan.
authors: Yosuke
authors: Y
authors: Hirotsu
authors: Department of Breast Surgery, Yamanashi Prefectural Central Hospital Kofu, Japan.
authors: Hiroshi
authors: H
authors: Nakagomi
authors: Department of Gynecology, Yamanashi Prefectural Central Hospital Kofu, Japan.
authors: Ikuko
authors: I
authors: Sakamoto
authors: Genome Analysis Center, Yamanashi Prefectural Central Hospital Kofu, Japan ; Pathology Division, Laboratory Department, Yamanashi Prefectural Central Hospital Kofu, Japan.
authors: Kenji
authors: K
authors: Amemiya
authors: Genome Analysis Center, Yamanashi Prefectural Central Hospital Kofu, Japan ; Department of Gastroenterology, Yamanashi Prefectural Central Hospital Kofu, Japan.
authors: Hitoshi
authors: H
authors: Mochizuki
authors: Genome Analysis Center, Yamanashi Prefectural Central Hospital Kofu, Japan ; Department of Gastroenterology, Yamanashi Prefectural Central Hospital Kofu, Japan ; Graduate School of Medicine, University of Tokyo Tokyo, Japan.
authors: Masao
authors: M
authors: Omata
keywords: BRCA1; BRCA2; Japanese; diagnostic; familial; next-generation sequencing