Comprehensive profiling of
            <i>BRCA1 and BRCA2</i>
            variants in breast and ovarian cancer in Chinese patients

Gao, Xianqi; Nan, Xiyan; Liu, Yilan; Li, Rui; Zang, Wanchun; Shan, Guangyu; Gai, Fei; Zhang, Jingfeng; Li, Lei; Cheng, Gang; Song, Lele

doi:10.1002/humu.23965

Cited by 20 publications

(23 citation statements)

References 36 publications

(40 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These differences may originate from the selection of subjects and the database used for analysis. As addressed in a recently published meta-analysis (47), the variant profile in ethnically Chinese people was distinctive from those in other ethnic groups with no distinct founder pathogenic variants. However, this conclusion should be treated cautiously.…”

Section: Discussionmentioning

confidence: 93%

Germline and Somatic BRCA1/2 Mutations in 172 Chinese Women With Epithelial Ovarian Cancer

You

et al. 2020

Front. Oncol.

Self Cite

View full text Add to dashboard Cite

Objective: Despite several nationwide cohort studies of germline BRCA1/2 mutations and several small cohort studies of somatic BRCA1/2 mutations in Chinese epithelial ovarian cancer (EOC) patients, little is known about the impact of these findings on survival outcomes in this population. In this study of 172 retrospectively recruited Chinese EOC patients, germline and somatic BRCA1/2 mutations and their value for predicting survival outcomes were evaluated. Methods: Unselected patients who visited the study center from January 1, 2011, to January 1, 2015, were recruited and asked to provide peripheral blood samples for this study if they were pathologically confirmed to have primary EOC. All patients received staging surgeries or debulking surgeries involving systemic platinum-based chemotherapy, and the patients were then followed up to December 1, 2017. DNA was extracted from formalin-fixed, paraffin-embedded (FFPE) sections and peripheral blood and sequenced for somatic and germline testing, respectively. The demographic and clinicopathological characteristics of the patients were collected to analyze the distribution of BRCA mutations in subgroups. Survival outcomes were compared among various BRCA mutation statuses using univariate and multivariate models. Results: In 58 (33.7%) patients, 63 variants were identified, including variants of unknown significance (VUS) in 18 patients (10.5%) and pathogenic or likely pathogenic variants in a partially overlapping set of 41 patients (23.8%). Germline BRCA mutations, somatic BRCA mutations, BRCA1 mutations in general, and BRCA2 mutations in general were found in 35 (20.3%), 7 (4.1%), 28 (16.3%), and 13 (7.6%) patients, respectively. Five recurrent mutations were identified. Personal and family cancer histories as well as hereditary breast and ovarian cancer (HBOC) criteria were associated with deleterious BRCA mutations both overall and in the germline specifically, whereas only age at diagnosis of EOC was associated with somatic BRCA mutations. In univariate and Cox regression analyses, patients with BRCA1/2 mutations in general had significant improvements in progression-free survival (PFS) and overall survival (OS). You et al. Germline and Somatic BRCA1/2 Mutations in EOC Conclusions: In Chinese EOC patients, the distributions and risk factors associated with germline and somatic BRCA1/2 mutations were similar to those previously reported in international studies. Deleterious BRCA mutations in general were associated with improved survival outcomes in this cohort.

show abstract

Section: Discussionmentioning

confidence: 93%

Germline and Somatic BRCA1/2 Mutations in 172 Chinese Women With Epithelial Ovarian Cancer

You

et al. 2020

Front. Oncol.

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

“…To date, several studies have reported the BRCA1/2 pathogenic variants from breast or ovarian cancer in Chinese populations with diverse results. A meta-analysis collected 94 publications with 2128 BRCA1/2 variant records which showed several high-frequency variants but no potential founder variants were identified [ 26 ], for example, the two highest recurrent variants c.5470_5477delATTGGGCA [ 27 – 29 ] in BRCA1 and c.3109C>T in BRCA2 [ 25 , 30 ]. Recently, You et al identified five recurrent variants in 172 Chinese women with epithelial ovarian cancer, including three pathogenic mutations ( BRCA1 c.5470_5477delATTGGGCA and c.66dup and BRCA2 c.1963delC) and two VUS missense mutations ( BRCA2 c.1568A>G and c.6325G>A) [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of Recurrent Variants in BRCA1 and BRCA2 across Multiple Cancers in the Chinese Population

Jiang

Tian

et al. 2020

BioMed Research International

View full text Add to dashboard Cite

BRCA1 and BRCA2 as important DNA repair genes have been thoroughly investigated in abundant studies. The potential relationships of BRCA1/2 pathogenic variants between multicancers have been verified in Caucasians but few in Chinese. In this study, we performed a two-stage study to screen BRCA1/2 pathogenic variants or variants of uncertain significance (VUS) with 7580 cancer cases and 4874 cancer-free controls, consisting of a discovery stage with 70 familial breast cancer cases and a subsequent validation stage with 7510 cases (3217 breast cancer, 1133 cervical cancer, 2044 hepatocellular carcinoma, and 1116 colorectal cancer). 48 variants were obtained from 70 familial breast cancer cases after BRCA1/2 exon detection, and finally, 20 pathogenic variants or VUS were selected for subsequent validation. Four recurrent variants in sporadic cases (BRCA1 c.4801A>T, BRCA1 c.3257del, BRCA1 c.440del, and BRCA2 c.7409dup) were identified and three of them were labeled Class 5 by ENIGMA. Two variants (BRCA1 c.3257del and c.440del) were specific in breast cancer cases, while BRCA2 c.7409dup and c.4307T>C were detected in two hepatocellular carcinoma patients and the BRCA1 c.4801A>T variant in one cervical cancer patient, respectively. Moreover, BRCA1 c.3257del was the most frequent variant observed in Chinese sporadic breast cancer and showed increased proliferation of BRCA1c.3257del-overexpressing triple-negative breast cancer cell lines (MDA-MB-231) in vitro. In addition to the known founder deleterious mutations, our findings highlight that the recurrently pathogenic variants in breast cancer cases could be taken as candidate genetic screening loci for a more efficient genetic screening of the Chinese population.

show abstract

“…Previous research has shown that pathogenic germline mutations increase the risk of cancers, including not only CRC 7 but also hereditary breast and ovarian cancer syndrome 9 and lung cancer 10 . However, this risk remains to be clearly defined for Chinese patients with CRC.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive characterization of CRC with germline mutations reveals a distinct somatic mutational landscape and elevated cancer risk in the Chinese population

et al. 2022

Self Cite

View full text Add to dashboard Cite

Objective: Hereditary colorectal cancer (CRC) accounts for approximately 5%–10% of all CRC cases. The full profile of CRC-relatedgermline mutations and the corresponding somatic mutational profile have not been fully determined in the Chinese population. Methods: We performed the first population study investigating the germline mutation status in more than 1,000 (n = 1,923) Chinesepatients with CRC and examined their relationship with the somatic mutational landscape. Germline alterations were examined witha 58-gene next-generation sequencing panel, and somatic alterations were examined with a 605-gene panel. Results: A total of 92 pathogenic (P) mutations were identified in 85 patients, and 81 likely pathogenic (LP) germline mutationswere identified in 62 patients, accounting for 7.6% (147/1,923) of all patients. MSH2 and APC was the most mutated gene in theLynch syndrome and non-Lynch syndrome groups, respectively. Patients with P/LP mutations had a significantly higher ratio ofmicrosatellite instability, highly deficient mismatch repair, family history of CRC, and lower age. The somatic mutational landscape revealed a significantly higher mutational frequency in the P group and a trend toward higher copy number variations in the non-Pgroup. The Lynch syndrome group had a significantly higher mutational frequency and tumor mutational burden than the non-Lynch syndrome group. Clustering analysis revealed that the Notch signaling pathway was uniquely clustered in the Lynch syndromegroup, and the MAPK and cAMP signaling pathways were uniquely clustered in the non-Lynch syndrome group. Population riskanalysis indicated that the overall odds ratio was 11.13 (95% CI: 8.289–15.44) for the P group and 20.68 (95% CI: 12.89–33.18) forthe LP group. Conclusions: Distinct features were revealed in Chinese patients with CRC with germline mutations. The Notch signaling pathwaywas uniquely clustered in the Lynch syndrome group, and the MAPK and cAMP signaling pathways were uniquely clustered in thenon-Lynch syndrome group. Patients with P/LP germline mutations exhibited higher CRC risk.

show abstract

Comprehensive profiling of BRCA1 and BRCA2 variants in breast and ovarian cancer in Chinese patients

Cited by 20 publications

References 36 publications

Germline and Somatic BRCA1/2 Mutations in 172 Chinese Women With Epithelial Ovarian Cancer

Germline and Somatic BRCA1/2 Mutations in 172 Chinese Women With Epithelial Ovarian Cancer

Identification of Recurrent Variants in BRCA1 and BRCA2 across Multiple Cancers in the Chinese Population

Comprehensive characterization of CRC with germline mutations reveals a distinct somatic mutational landscape and elevated cancer risk in the Chinese population

Contact Info

Product

Resources

About