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Prevalence and clinical significance of BRCA1/2 germline and somatic mutations in Taiwanese patients with ovarian cancer.

作者信息

Chao Angel, Chang Ting-Chang, Lapke Nina, Jung Shih-Ming, Chi Peter, Chen Chien-Hung, Yang Lan-Yan, Lin Cheng-Tao, Huang Huei-Jean, Chou Hung-Hsueh, Liou Jui-Der, Chen Shu-Jen, Wang Tzu-Hao, Lai Chyong-Huey

机构信息

Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan.

Gynecologic Cancer Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.

出版信息

Oncotarget. 2016 Dec 20;7(51):85529-85541. doi: 10.18632/oncotarget.13456.


DOI:10.18632/oncotarget.13456
PMID:27907908
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5356755/
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.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3218/5356755/74b279b976ba/oncotarget-07-85529-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3218/5356755/103823d302b6/oncotarget-07-85529-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3218/5356755/1bd741ab1a38/oncotarget-07-85529-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3218/5356755/74b279b976ba/oncotarget-07-85529-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3218/5356755/103823d302b6/oncotarget-07-85529-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3218/5356755/1bd741ab1a38/oncotarget-07-85529-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3218/5356755/74b279b976ba/oncotarget-07-85529-g003.jpg

相似文献

[1]
Prevalence and clinical significance of BRCA1/2 germline and somatic mutations in Taiwanese patients with ovarian cancer.

Oncotarget. 2016-12-20

[2]
Mutation landscape of germline and somatic BRCA1/2 in patients with high-grade serous ovarian cancer.

BMC Cancer. 2020-3-12

[3]
BRCA1/2 somatic mutation detection in formalin-fixed paraffin embedded tissue by next-generation sequencing in Korean ovarian cancer patients.

Pathol Res Pract. 2019-8-16

[4]
BRCA somatic and germline mutation detection in paraffin embedded ovarian cancers by next-generation sequencing.

Oncotarget. 2016-1-12

[5]
Recurrent BRCA1 Mutation, but no BRCA2 Mutation, in Vietnamese Patients with Ovarian Carcinoma Detected with Next Generation Sequencing.

Asian Pac J Cancer Prev. 2020-8-1

[6]
Targeted capture-based NGS is superior to multiplex PCR-based NGS for hereditary BRCA1 and BRCA2 gene analysis in FFPE tumor samples.

BMC Cancer. 2019-4-27

[7]
Validation of multi-gene panel next-generation sequencing for the detection of BRCA mutation in formalin-fixed, paraffin-embedded epithelial ovarian cancer tissues.

Taiwan J Obstet Gynecol. 2023-1

[8]
BRCA1 and BRCA2 mutations and clinical interpretation in 398 ovarian cancer patients: comparison with breast cancer variants in a similar population.

Hum Genomics. 2018-8-13

[9]
BRCA germline mutations in an unselected nationwide cohort of Chinese patients with ovarian cancer and healthy controls.

Gynecol Oncol. 2018-8-2

[10]
Detection of somatic BRCA1/2 mutations in ovarian cancer - next-generation sequencing analysis of 100 cases.

Cancer Med. 2016-7

引用本文的文献

[1]
Multigene germline and somatic testing for epithelial ovarian cancer in China.

NPJ Precis Oncol. 2025-8-13

[2]
Metformin sensitizes triple-negative breast cancer to histone deacetylase inhibitors by targeting FGFR4.

J Biomed Sci. 2025-3-17

[3]
Epidemiology and Mortality of Ovarian Cancer in Taiwan: A Population-Based Study.

J Clin Med. 2022-9-24

[4]
Next-generation sequencing based detection of and large genomic rearrangements in Chinese cancer patients.

Front Oncol. 2022-9-6

[5]
Germline variants profiling of BRCA1 and BRCA2 in Chinese Hakka breast and ovarian cancer patients.

BMC Cancer. 2022-8-2

[6]
Prevalence of Pathogenic Germline Variants and Their Association with Clinical Characteristics in Patients with Epithelial Ovarian Cancer in a Rural Area of Japan.

Genes (Basel). 2022-6-18

[7]
Germline mutations in Chinese ovarian cancer with or without breast cancer.

Mol Genet Genomic Med. 2022-7

[8]
Prevalence of BRCA1 and BRCA2 pathogenic sequence variants in ovarian cancer patients in the Gulf region: the PREDICT study.

BMC Cancer. 2021-12-20

[9]
Prevalence and clinical characterization of BRCA1 and BRCA2 mutations in Korean patients with epithelial ovarian cancer.

Cancer Sci. 2021-12

[10]
and Variation in Taiwanese General Population and the Cancer Cohort.

Front Mol Biosci. 2021-6-21

本文引用的文献

[1]
Hereditary breast and ovarian cancer: new genes in confined pathways.

Nat Rev Cancer. 2016-8-12

[2]
Prevalence and spectrum of BRCA germline variants in mainland Chinese familial breast and ovarian cancer patients.

Oncotarget. 2016-2-23

[3]
BRCA somatic and germline mutation detection in paraffin embedded ovarian cancers by next-generation sequencing.

Oncotarget. 2016-1-12

[4]
Efficacy and safety of olaparib monotherapy in germline BRCA1/2 mutation carriers with advanced ovarian cancer and three or more lines of prior therapy.

Gynecol Oncol. 2016-2

[5]
Inherited Mutations in Women With Ovarian Carcinoma.

JAMA Oncol. 2016-4

[6]
Evaluation of germline BRCA1 and BRCA2 mutations in a multi-ethnic Asian cohort of ovarian cancer patients.

Gynecol Oncol. 2016-5

[7]
BRCA1 and BRCA2 mutations in Japanese patients with ovarian, fallopian tube, and primary peritoneal cancer.

Cancer. 2016-1-1

[8]
Germline Mutations of BRCA1 and BRCA2 in Korean Ovarian Cancer Patients: Finding Founder Mutations.

Int J Gynecol Cancer. 2015-10

[9]
Haploinsufficiency for BRCA1 leads to cell-type-specific genomic instability and premature senescence.

Nat Commun. 2015-6-24

[10]
Association of type and location of BRCA1 and BRCA2 mutations with risk of breast and ovarian cancer.

JAMA. 2015-4-7

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