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

Li, Ang; Xie, Rong; Zhi, Qihuan; Deng, Yixiao; Wu, Yinong; Li, Weiwei; Yang, Lu; Jiao, Zinan; Luo, Jiaqi; Zi, Yi; Gang, Sun; Zhang, Jiajia; Shi, Yujian; Liu, Jian

doi:10.1016/j.ygyno.2018.07.024

Cited by 38 publications

(46 citation statements)

References 31 publications

(39 reference statements)

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“…The mutation rate of BRCA1/2 in our ovarian cancer subgroup was slightly higher than that in other studies that found BRCA1/2 deleterious mutations with rates of 13% to 15% . Overall, BRCA1/2 mutation accounted for 86% of total mutations in hereditary ovarian cancer, and the BRCA1 mutation rate was more pronounced than the BRCA2 in ovarian cancer patients, which is similar to the results from both Li et al (2018, n = 1331, BRCA1 for 17.1% and BRCA2 for 5.3%) and Norquist et al (2016, n = 1915, BRCA1 for 9.5% and BRCA2 for 5.1%). Apart from the B RCA1/2 mutation, 0.9% of the subgroup carried BRIP1 mutation (BRCA1‐interacting protein C‐terminal helicase 1), which is comparable to other studies in which the prevalence ranges from 0.8% to 1.5% .…”

Section: Discussionsupporting

confidence: 87%

Prevalence of hereditary breast and ovarian cancer (HBOC) predisposition gene mutations among 882 HBOC high‐risk Chinese individuals

et al. 2019

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This is an open access article under the terms of the Creat ive Commo ns Attri bution-NonCo mmercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. AbstractIdentification of deleterious variants in hereditary breast and ovarian cancer (HBOC) susceptibility genes allows for increased clinical surveillance and early detection, and could predict the response to poly (ADP-ribose) polymerase (PARP) inhibitor in patients with advanced ovarian carcinomas. To determine the prevalence and clinical prediction factors for HBOC syndrome, 882 selected individuals underwent multigene panel testing for HBOC risk assessment during the period from January 2015 to March 2018. Overall, 176 deleterious mutations were observed in 19.50% (n = 172) of individuals. Twenty-six of 176 mutations could not be retrieved in related public databases and were considered to be novel. Among patients with ovarian cancer, 115 deleterious mutations were identified in 429 patients (48.6%) with significant enrichment for a family history of breast or ovarian cancer syndrome (P < .05). In the breast cancer subgroup, 31 deleterious mutations were identified in 261 patients. Besides BRCA1 (8; 25.8%) and BRCA2 (11; 35.5%), the most frequently occurring genes, an additional 12 deleterious mutations (38.7%) were found in seven other susceptibility genes. Higher mutation incidence (57.9%) was observed in subjects with histories of breast and ovarian cancer. Our results highlighted the genetic heterogeneity of HBOC and the efficiency of a multigene panel in carrying out risk assessment. K E Y W O R D S BRCA1, BRCA2, HBOC, mutation, NGS | INTRODUC TI ONBreast and ovarian cancers fiercely impact health of Chinese women as well as their families. 1,2 As is known, these two diseases are heritable. Inherited mutations of BRCA1 and BRCA2 are pathogenetic in a majority of HBOC patients. 3,4 In addition to BRCA1/2, genetic alterations of other HR genes (ATM, BRIP1, CHEK2, RAD50, RAD51C) are also associated with HBOC. 5-8 Moreover, research

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Section: Discussionsupporting

confidence: 87%

Prevalence of hereditary breast and ovarian cancer (HBOC) predisposition gene mutations among 882 HBOC high‐risk Chinese individuals

et al. 2019

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“…The frequency of BRCA1/2 mutations was 23.07% in the ovarian cancer only subgroup, 15.38% for BRCA1 and 7.69% for BRCA2. Overall, BRCA1/2 accounted for 86% in hereditary ovarian cancer, and the BRCA1 mutation rate was more pronounced than the BRCA2 mutation rate in ovarian cancer patients, similar to both Ang Li et al (22) (2018, n = 1331, BRCA1 for 17.1% and BRCA2 for 5.3%) and Norquist et al (23) (2016, n = 1915, BRCA1 for 9.5% and BRCA2 for 5.1%). Interestingly and noteworthy, ovarian cancer carried BRCA1/2 mutations in China was slightly higher than expected.…”

Section: Comparison Of Mutation Frequency With Previous Studiessupporting

confidence: 75%

Frequency of mutations in 21 hereditary breast and ovarian cancer susceptibility genes among high-risk Chinese individuals

Шао

Cheng

Guo

et al. 2019

Preprint

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are employees of BGI Genomics that produces the 21gene panel test used in this study. Translational relevanceMultiple high-and moderate-penetrance genes (including BRCA1 and BRCA2) have been discovered as susceptibility genes for hereditary breast and ovarian cancer. Recent advances in next generation sequencing (NGS) have provided an efficient method to evaluate these susceptibility genes simultaneously. We assessed the frequency of mutations in 21 susceptibility genes in a large cohort of subjects who were referred for genetic testing. The cohort is from several comprehensive hospitals with a wide geographical distribution representing the overall situation of the Chinese population. The prevalence of mutations in this population has been rarely reported in previous studies. Our results reflect the mutation frequency in individuals defined by guidelines and have great clinical practical significance. AbstractPurpose: To determine the prevalence and clinical prediction factors associated with deleterious mutations among 882 high-risk Chinese individuals who underwent multigene panel testing for hereditary breast and ovarian cancer (HBOC) risk assessment.Experimental Design: Subjects were selected from individuals referred for genetic testing using a 21-gene panel (Oseq-BRCA) between January 2015 and March 2018. The distribution and prevalence of deleterious mutations were analyzed for the full cohort as well as subtypes. Results:Overall, 176 deleterious mutations were observed in 19.50% (n = 172) individuals. Of these, 26 mutations are not reported in public databases and literatures. In the ovarian cancer only subgroup, 115 deleterious mutations were identified in 429 patients (48.6%). Patients with ovarian cancer with mutations were enriched for a family history of breast or ovarian cancers (p < 0.05). In the breast cancer only subgroup, 31 deleterious mutations were identified in 261 patients. Most mutations occurred in BRCA1 (8; 25.8%) and BRCA2 (11; 35.5%). An additional 12 deleterious mutations (38.7%) were found in 7 other susceptibility genes. An increased frequency of mutation rate (57.9%) was observed in the subgroup of subjects with histories of both breast and ovarian cancer.Conclusions: 19.50% of individuals carried a deleterious mutation in HBOC susceptibility genes in our cohort. Subgroup of subjects with histories of both breast and ovarian cancer had the highest prevalence of mutations. Our results highlighted the genetic heterogeneity of HBOC and the efficiency of multigene panel in performing risk assessment.

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“…Previously, BRCA1 c.5470_5477del was reported as a high‐frequency recurrent pathogenic variant in Chinese BC patients and ovarian cancer patients . Only one previous study performed a haplotype analysis for BRCA1 c.5470_5477del, in which three independent families shared the same haplotype, whereas two additional BC patients had similar but not exactly the same haplotype .…”

Section: Discussionmentioning

confidence: 99%

“…Previously, BRCA1 c.5470_5477del was reported as a highfrequency recurrent pathogenic variant in Chinese BC patients and ovarian cancer patients. 16,19,24 Only one previous study performed a haplotype analysis for BRCA1 c.5470_5477del, in which three independent families shared the same haplotype, whereas two additional BC patients had similar but not exactly the same haplotype. 16 Because of the small sample size (n = 489) and mixed ethnicity of the subjects, this previous study was not sufficient to demonstrate whether BRCA1 c.5470_5477del is a Chinese Han founder mutation.…”

Section: Discussionmentioning

confidence: 99%

BRCA1 c.5470_5477del, a founder mutation in Chinese Han breast cancer patients

Meng

Yao

Yuan

et al. 2020

Intl Journal of Cancer

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The spectrum and frequency of BRCA1/2 pathogenic variants may be ethnicity‐specific. Whether high‐frequency founder mutations are present in Chinese women remains largely unknown. In the current study, germline pathogenic variants in the BRCA1/2 genes were determined in 9,505 unselected Chinese Han breast cancer (BC) patients by next‐generation and/ or Sanger sequencing. Four hundred and seventy‐one (5.0%) BC patients carried BRCA1/2 pathogenic variants in this cohort. A total of 25 recurrent pathogenic variants (at least found in four unrelated patients) were identified in this cohort (8 BRCA1 and 17 BRCA2 recurrent pathogenic variants), 161 patients carried one of these recurrent pathogenic variants in this cohort of 9,505 patients. All of these 25 recurrent pathogenic variants were further explored whether they had founder effect through haplotype analysis. The most common pathogenic variant, BRCA1 c.5470_5477del, was found in 30 BC patients from 29 unrelated families. Twenty‐seven of these 29 unrelated patients who carried this BRCA1 c.5470_5477del mutation shared an identical haplotype, indicating that BRCA1 c.5470_5477del was a founder mutation in the Chinese Han population. Furthermore, BRCA1 c.5470_5477del mutation carriers had a significantly worse survival than noncarriers (disease‐free survival, p = 0.049; overall survival, p = 0.029). Taken together, our data suggested that BRCA1 c.5470_5477del is a founder mutation in the Chinese Han population and BRCA1 c.5470_5477del mutation carriers have a poor survival.

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

Abstract: We recommend BRCA testing to all Chinese OC patients and those general Chinese who have family members with hereditary breast and ovarian related cancer (HBOC)-related cancers. Variants carriers would not only benefit from early prevention of OC but also for the medical management.

Cited by 38 publications

References 31 publications

Prevalence of hereditary breast and ovarian cancer (HBOC) predisposition gene mutations among 882 HBOC high‐risk Chinese individuals

Prevalence of hereditary breast and ovarian cancer (HBOC) predisposition gene mutations among 882 HBOC high‐risk Chinese individuals

Frequency of mutations in 21 hereditary breast and ovarian cancer susceptibility genes among high-risk Chinese individuals

BRCA1 c.5470_5477del, a founder mutation in Chinese Han breast cancer patients

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