title: Prevalence and clinical significance of BRCA1/2 germline and somatic mutations in Taiwanese patients with ovarian cancer.
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.
authors.affiliation: Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan.|Gynecologic Cancer Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Angel
authors.initials: A
authors.lastname: Chao
authors.affiliation: Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan.|Gynecologic Cancer Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Ting-Chang
authors.initials: TC
authors.lastname: Chang
authors.affiliation: ACTGenomics, Co. Ltd., Taiwan.
authors.forename: Nina
authors.initials: N
authors.lastname: Lapke
authors.affiliation: Department of Pathology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan.
authors.forename: Shih-Ming
authors.initials: SM
authors.lastname: Jung
authors.affiliation: Institute of Biochemical Sciences, College of Life Science, National Taiwan University, Taiwan.
authors.forename: Peter
authors.initials: P
authors.lastname: Chi
authors.affiliation: ACTGenomics, Co. Ltd., Taiwan.
authors.forename: Chien-Hung
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Clinical Trial Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Lan-Yan
authors.initials: LY
authors.lastname: Yang
authors.affiliation: Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan.|Gynecologic Cancer Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Cheng-Tao
authors.initials: CT
authors.lastname: Lin
authors.affiliation: Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan.|Gynecologic Cancer Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Huei-Jean
authors.initials: HJ
authors.lastname: Huang
authors.affiliation: Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan.|Gynecologic Cancer Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Hung-Hsueh
authors.initials: HH
authors.lastname: Chou
authors.affiliation: Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan.|Gynecologic Cancer Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Jui-Der
authors.initials: JD
authors.lastname: Liou
authors.affiliation: ACTGenomics, Co. Ltd., Taiwan.
authors.forename: Shu-Jen
authors.initials: SJ
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan.|Gynecologic Cancer Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.|School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Tzu-Hao
authors.initials: TH
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan.|Gynecologic Cancer Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Chyong-Huey
authors.initials: CH
authors.lastname: Lai
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001706:Biopsy; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D005404:Fixatives / Q000737:chemistry; D005557:Formaldehyde / Q000737:chemistry; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D019656:Loss of Heterozygosity; D008875:Middle Aged; D017720:Molecular Epidemiology; D010051:Ovarian Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D016612:Paraffin Embedding; D010641:Phenotype; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology; D016707:Tissue Fixation; D055815:Young Adult
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D005404:Fixatives; D005557:Formaldehyde
keywords: BRCA1/2; germline mutations; ovarian cancer; somatic mutations