N25: Frequency Of Germline Pathogenic Variants Of Cancer Susceptibility Genes For Japanese Ovarian Cancer Patients

A. Hirasawa1, 2, I. Imoto3, T. Naruto4, T. Akahane2, W. Yamagami2, H. Nomura2, K. Masuda4, N. Susumu2, 5, H. Tsuda6, D. Aoki2

1 – Dept. Clin. Genomic. Med, Okayama Univ., Med. Sch. 2 – Dep. Obst. & Gyne., Keio Univ., Sch. Med. 3 – Risk Assess. Cent, Aichi Can. Cent. Hos. 4 – Dep. Hum. Genet, Grad. Sch. Biomed Sci, Tokushima Univ. 5 – Dep. Obst. & Gyne.,  International. Univ Health & Welfare. 6 – Dep. Basic Pathol.  National Defense Med.


Aim: The aim of our study was to reveal the prevalence of pathogenic germline variants of candidate genes associated with genetic predisposition to ovarian cancer (OC)  in Japanese OC patients.

Method: Germ-line DNA samples from 230 unselected OC patients were recruited from the Keio Women’s Health Biobank at Keio University School of Medicine. 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 were classified according to the American College of Medical Genetics and Genomics recommendations. Furthermore, BRCA1/2 variants were interpreted using resources from Myriad Genetic Laboratories.

Results: Of 230 patients, 19 (8.3%) and 8 cases (3.5%) carried germline BRCA1 and BRCA2 pathogenic variants, respectively. No variant of uncertain significance (VUS) of BRCA1/2 genes was detected in our analysis according to the database of Myriad Genetics. Six (2.6%) carried pathogenic germline variants of mismatch repair genes. Carriers of BRCA1/2 or pathogenic variants of any other genes tested 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).

Conclusion: Our data can facilitate genetic predisposition prediction in Japanese OC patients and referring high-risk patients for genetic counseling and testing.