Prevalence and clinical significance of BRCA1/2 germline and somatic mutations in Taiwanese patients with ovarian cancer
Journal
Oncotarget
Journal Volume
7
Journal Issue
51
Pages
85529-85541
Date Issued
2016
Author(s)
A. Chao
T. C. Chang
N. Lapke
S. M. Jung
C. H. Chen
L. Y. Yang
C. T. Lin
H. J. Huang
H. H. Chou
J. D. Liou
S. J. Chen
T. H. Wang
C. H. Lai
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.
Subjects
BRCA1/2; Germline mutations; Ovarian cancer; Somatic mutations
SDGs
Other Subjects
BRCA1 protein; BRCA2 protein; formaldehyde; paraffin; BRCA1 protein; BRCA1 protein, human; BRCA2 protein; BRCA2 protein, human; fixative; adult; aged; Article; carcinogenicity; clear cell carcinoma; controlled study; endometrioid carcinoma; female; gene identification; gene inactivation; genetic variability; germline mutation; heterozygosity loss; human; human cell; human tissue; major clinical study; middle aged; mutation rate; mutational analysis; next generation sequencing; ovary cancer; ovary carcinoma; prevalence; serous ovarian carcinoma; somatic mutation; Taiwanese; treatment planning; tumor suppressor gene; very elderly; Asian continental ancestry group; biopsy; chemistry; dna mutational analysis; epidemiology; ethnology; genetic predisposition; genetics; high throughput sequencing; molecular epidemiology; ovary tumor; pathology; phenotype; procedures; risk factor; Taiwan; tissue fixation; young adult; Adult; Aged; Aged, 80 and over; Asian Continental Ancestry Group; Biopsy; BRCA1 Protein; BRCA2 Protein; DNA Mutational Analysis; Female; Fixatives; Formaldehyde; Genetic Predisposition to Disease; Germ-Line Mutation; High-Throughput Nucleotide Sequencing; Humans; Loss of Heterozygosity; Middle Aged; Molecular Epidemiology; Ovarian Neoplasms; Paraffin Embedding; Phenotype; Risk Factors; Taiwan; Tissue Fixation; Young Adult
Type
journal article