TY - JOUR
T1 - Prevalence of pathogenic germline variants detected by multigene sequencing in unselected Japanese patients with ovarian cancer
AU - Hirasawa, Akira
AU - Imoto, Issei
AU - Naruto, Takuya
AU - Akahane, Tomoko
AU - Yamagami, Wataru
AU - Nomura, Hiroyuki
AU - Masuda, Kiyoshi
AU - Susumu, Nobuyuki
AU - Tsuda, Hitoshi
AU - Aoki, Daisuke
N1 - Funding Information:
We thank the patients and the supporting medical staff for making this study possible. We are grateful to FALCO Biosystems Ltd. for providing scientific and technical advice. We also thank Professor Kenjiro Kosaki, Dr. Kokichi Sugano, Dr. Arisa Ueki, and Ms. Kumiko Misu for their support in the genetic counseling clinic. We are also grateful to Ms. Tomomi Noda, Ms. Mika Okabe, and Ms. Atsuko Fukushima for their biobank and data management. This study was supported in part by AstraZeneca Externally Sponsored Scientific Research (ESR), Japan Society for the Promotion of Science (JSPS) KAKENHI grant numbers 17K19611 and 16K15618, JSPS Bilateral programs, Keio Gijuku Academic Development Funds from Keio University, and the Japan Agency for Medical Research and Development grant; Public Understanding and Information Sharing on Research Ethics (Ethical, legal and social issues on the practical application of genome medicine).
Funding Information:
This study was supported in part by AstraZeneca Externally Sponsored Scientific Research (ESR), Japan Society for the Promotion of Science (JSPS) KAKENHI grant numbers 17K19611 and 16K15618, JSPS Bilateral programs, Keio Gijuku Academic Development Funds from Keio University, and the Japan Agency for Medical Research and Development grant; Public Understanding and Information Sharing on Research Ethics (Ethical, legal and social issues on the practical application of genome medicine).
Publisher Copyright:
© Hirasawa et al.
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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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U2 - 10.18632/oncotarget.22733
DO - 10.18632/oncotarget.22733
M3 - Article
C2 - 29348823
AN - SCOPUS:85038855287
SN - 1949-2553
VL - 8
SP - 112258
EP - 112267
JO - Oncotarget
JF - Oncotarget
IS - 68
ER -