Prevalence and clinical significance ofBRCA1/2germline and somatic mutations in Taiwanese patients with ovarian cancer

// Angel Chao 1, 2, * , Ting-Chang Chang 1, 2, * , Nina Lapke 3, * , Shih-Ming Jung 4 , Peter Chi 5 , Chien-Hung Chen 3 , Lan-Yan Yang 6 , Cheng-Tao Lin 1, 2 , Huei-Jean Huang 1, 2 , Hung-Hsueh Chou 1, 2 , Jui-Der Liou 1, 2 , Shu-Jen Chen 3 , Tzu-Hao Wang 1, 2, 7 , Chyong-Huey Lai 1, 2 1 Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan 2 Gynecologic Cancer Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan 3 ACTGenomics, Co. Ltd., Taiwan 4 Department of Pathology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan 5 Institute of Biochemical Sciences, College of Life Science, National Taiwan University, Taiwan 6 Clinical Trial Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan 7 School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan * These authors have contributed equally to this work Correspondence to: Shu-Jen Chen, email: sjchen@actgenomics.com Tzu-Hao Wang, email: knoxtn@cgmh.org.tw Chyong-Huey Lai, email: laich46@cgmh.org.tw Keywords: BRCA1/2, germline mutations, somatic mutations, ovarian cancer Received: August 20, 2016      Accepted: October 28, 2016      Published: November 19, 2016 ABSTRACT Germline and somatic BRCA1/2 mutations define a subset of patients with ovarian cancer who may benefit from treatment with poly (ADP-ribose) polymerase inhibitors. Unfortunately, data on the frequency of BRCA1/2 germline mutations in Taiwanese patients with ovarian cancer are scarce, with the prevalence of somatic mutations being unknown. We aim to investigate the occurrence of BRCA1/2 mutations in 99 Taiwanese patients with ovarian cancer which included serous (n = 46), endometrioid (n = 24), and clear cell (n = 29) carcinomas. BRCA1/2 mutations were identified using next-generation sequencing of formalin-fixed paraffin-embedded tumor samples. Pathogenic variants ( BRCA1 : n = 7; BRCA2 : n = 6) were detected in 12.1% (12/99) of the study patients. Somatic and germline BRCA1/2 mutation rates in serous ovarian cancer are 4/46 (8.7%) and 8/46 (17%), respectively. All of the pathogenic BRCA1/2 mutations were identified in serous carcinoma samples (12/46; 26.1%). One-third (4/12) of the deleterious BRCA1/2 mutations occurred in tumor tissues only (somatic mutations). All of them coexisted with loss of heterozygosity, resulting in biallelic BRCA inactivation. Five novel pathogenic mutations were identified, including four somatic variants ( BRCA1 p.S242fs, BRCA1 p.F989fs, BRCA1 p.G1738fs, and BRCA2 p.D1451fs) and a germline variant ( BRCA2 p.E260fs). We also detected additional six novel mutations (three in BRCA1 and three in BRCA2) with pathogenic potentials. We conclude that BRCA1/2 mutations are common in Taiwanese patients with serous ovarian carcinoma and similar to mutation rates in other ethnic groups. The analysis of BRCA1/2 somatic mutations is crucial for guiding therapeutic decisions in ovarian cancer.