Abstract 4274: The contribution of deleterious germ-line mutations of susceptibility genes to ovarian, fallopian tube, and peritoneal cancers in Japanese
Authors: Hirasawa Akira , Imoto Issei , Naruto Takuya , Akahane Tomoko , Yamagami Wataru , Susumu Nobuyuki , Tsuda Hitoshi , Aoki Daisuke 
Published: July 2017

Different ethnic groups present specific morphological features in ovarian cancer (OC). High-grade serous OC is more frequently found in Caucasian women, in contrast clear cell OC is more frequently found in East Asian women. Although inherited mutations of BRCA1 or BRCA2 (BRCA1/2) and other genes are known to predispose to OC, the contributions of these inherited mutations on disease burden is not well characterized in Japanese OC patients. Using a comprehensive genetic testing panel, the aim of our study was to identify the prevalence of pathogenic germ-line mutations of candidate genes associated with genetic predisposition to OC in Japanese patients with ovarian, fallopian tube, or peritoneal cancer.Samples from 236 individuals with unselected ovarian, fallopian tube, or peritoneal cancer, which were obtained from the Keio Women’s Health Biobank (KWB) from the School of Medicine at Keio University (Tokyo, Japan), were used for this study. Germ-line DNA was enriched using the SureSelect XT Target Enrichment System (Agilent Technologies) designed for 75 or 79 genes as a custom OC panel, followed by sequencing using MiSeq (Illumina). Detected variants, including point mutations, small indels, and a gross deletion, were classified according to the American College of Medical Genetics and Genomics (ACMG) recommendations. Furthermore, BRCA1/2 variants were interpreted using resources from Myriad Genetic Laboratories.Forty-two (17.8%) OC patients had germ-line mutations of cancer predisposition genes. BRCA1/2 pathological germ-line mutations were found in 27 cases (11.4%) while six cases (2.5%) had a mutation in a mismatch repair gene (MLH1, MSH2, MSH6, or PMS2). Furthermore, ten cases (4.2%) had germ-line mutations in the RAD51D, ATM, MRE11A, FANCC, or GABRA2 genes. Of patients with a BRCA1/2 mutation (n=27), we found that the most common histological subtype was high-grade serous OC, but we also found two cases with clear cell carcinoma. Of 42 cases with an inherited mutation, we found that 25% (6/24) had no family history of cancer, and 78% (31/41) were under 60 years old at diagnosis.We found that approximately 18% of unselected Japanese patients with ovarian, fallopian tube, or peritoneal cancer were associated with inherited mutations of cancer-predisposing genes. Our study demonstrates that comprehensive genetic testing is informative for all women with ovarian, fallopian tube, and peritoneal cancers to establish personalized clinical management and genetic counseling, irrespective of the patient's histological subtypes, ages or family histories.

Citation Format: Akira Hirasawa, Issei Imoto, Takuya Naruto, Tomoko Akahane, Wataru Yamagami, Nobuyuki Susumu, Hitoshi Tsuda, Daisuke Aoki. The contribution of deleterious germ-line mutations of susceptibility genes to ovarian, fallopian tube, and peritoneal cancers in Japanese [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4274. doi:10.1158/1538-7445.AM2017-4274