Research Papers:

Prevalence of pathogenic germline variants detected by multigene sequencing in unselected Japanese patients with ovarian cancer

Akira Hirasawa _, Issei Imoto, Takuya Naruto, Tomoko Akahane, Wataru Yamagami, Hiroyuki Nomura, Kiyoshi Masuda, Nobuyuki Susumu, Hitoshi Tsuda and Daisuke Aoki

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Oncotarget. 2017; 8:112258-112267. https://doi.org/10.18632/oncotarget.22733

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Akira Hirasawa1, Issei Imoto2, Takuya Naruto2, Tomoko Akahane1, Wataru Yamagami1, Hiroyuki Nomura1, Kiyoshi Masuda2, Nobuyuki Susumu1,3, Hitoshi Tsuda4 and Daisuke Aoki1

1Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan

2Department of Human Genetics, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan

3Department of Obstetrics and Gynecology, International University of Health and Welfare, Chiba, Japan

4Department of Basic Pathology, National Defense Medical College, Saitama, Japan

Correspondence to:

Akira Hirasawa, email: [email protected]

Issei Imoto, email: [email protected]

Keywords: ovarian cancer; germline; pathogenic variant; multigene panel; Japanese women

Received: September 11, 2017     Accepted: November 13, 2017     Published: November 28, 2017


Pathogenic germline BRCA1, BRCA2 (BRCA1/2), and several other gene variants predispose women to primary ovarian, fallopian tube, and peritoneal carcinoma (OC), although variant frequency and relevance information is scarce in Japanese women with OC. Using targeted panel sequencing, we screened 230 unselected Japanese women with OC from our hospital-based cohort for pathogenic germline variants in 75 or 79 OC-associated genes. Pathogenic variants of 11 genes were identified in 41 (17.8%) women: 19 (8.3%; BRCA1), 8 (3.5%; BRCA2), 6 (2.6%; mismatch repair genes), 3 (1.3%; RAD51D), 2 (0.9%; ATM), 1 (0.4%; MRE11A), 1 (FANCC), and 1 (GABRA6). Carriers of BRCA1/2 or any other tested gene pathogenic variants were more likely to be diagnosed younger, have first or second-degree relatives with OC, and have OC classified as high-grade serous carcinoma (HGSC). After adjustment for these variables, all 3 features were independent predictive factors for pathogenic variants in any tested genes whereas only the latter two remained for variants in BRCA1/2. Our data indicate similar variant prevalence in Japanese patients with OC and other ethnic groups and suggest that HGSC and OC family history may facilitate genetic predisposition prediction in Japanese patients with OC and referring high-risk patients for genetic counseling and testing.

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