Identification of BRCA1:c.5470_5477del as a Founder Mutation in Chinese Ovarian Cancer Patients

Li, Jun; Han, Sile; Zhang, Cuiyun; Luo, Yanlin; Wang, Li; Wang, Ping; Wang, Yi; Xia, Qingxin; Wang, Xiaoyan; Wei, Bing; Ma, Jie; Li, Hongle; Guo, Yongjun

doi:10.3389/fonc.2021.655709

Cited by 4 publications

(5 citation statements)

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“…Wang et al also found that BRCA1 c.5470_5477del was highly prevalent in a population of Chinese women population [ 46 ]. Studies have shown that BRCA1 c.5470_5477del was a founder mutation in Chinese Han ovarian cancer patients [ 47 ] and Chinese Han breast cancer patients [ 48 ]. A meta-analysis conducted by Kim et al on population samples from mainland China in 2016 found that BRCA1 c.981_982delAT and BRCA2 c.3195_3198delTAAT were highly prevalent in mainland Chinese population [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

“…BRCA1 c.4065_4068del has been detected in some populations [61][62][63]. Another study showed that c.4065_4068del is one of the three most common BRCA1 variants in Chinese ovarian cancer patients [47]. In the BRCA2 gene, c.5164_5165delAG has been detected in the Chinese Han population [64], Macau population [65], and Taiwanese populations [66].…”

Section: Discussionmentioning

confidence: 99%

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

Zhang

et al. 2022

BMC Cancer

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Objective To investigate the prevalence and spectrum of BRCA1 and BRCA2 mutations in Chinese Hakka patients with breast and ovarian cancer. Methods A total of 1,664 breast or ovarian cancer patients were enrolled for genetic testing at our hospital. Germline mutations of the BRCA gene were analysed by next-generation sequencing, including the coding regions and exon intron boundary regions. Results The 1,664 patients included 1,415 (85.04%) breast cancer patients and 245 (14.72%) ovarian cancer patients, while four (0.24%) patients had both the breast and ovarian cancers. A total of 151 variants, including 71 BRCA1 variants and 80 BRCA2 variants, were detected in the 234 (14.06%) patients. The 151 variants included 58 pathogenic variants, 8 likely pathogenic variants, and 85 variants of unknown significance (VUS). A total of 56.25% (18/32) and 65.38% (17/26) of pathogenic variants (likely pathogenic variants are not included) were distributed in exon 14 of BRCA1 and exon 11 of BRCA2, respectively. The most common pathogenic variants among this Hakka population are c.2635G > T (p.Glu879*) (n = 7) in the BRCA1 gene and c.5164_5165del (p.Ser1722Tyrfs*4) (n = 7) in the BRCA2 gene among the Hakka population. A hotspot mutation in the Chinese population, the BRCA1 c.5470_5477del variant was not found in this Hakka population. The prevalence and spectrum of variants in the BRCA genes in the Hakka patients are different from that in other ethnic groups. Conclusions The most common pathogenic variant in this population is c.2635G > T in the BRCA1 gene, and c.5164_5165delAG in the BRCA2 gene in this population. The prevalence and spectrum of variants in the BRCA1 and BRCA2 genes in the Hakka patients from southern China are different from those in other ethnic groups.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Zhang

et al. 2022

BMC Cancer

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“…A total of 25 BRCA1 deleterious variants were detected in 29 patients, including 25 (25/29, 86.2%) protein-truncating (15 frameshift and 10 nonsense), 2 (2/29, 6.9%) missense, 1 (1/29, 3.4%) start lost, and 1 (1/29, 3.4%) E15 deletion. The most frequent variant in BRCA1 was c.5470_5477del (p.I1824Dfs*3, n = 3), which was considered a founder variant in the Chinese Han patients with BC or ovarian cancer [ 13 , 14 ]. Other recurrent BRCA1 variants were c.2998G > T (p.E1000*, n = 2) and c.228_229delinsAAAGTG (p.S76Rfs*6, n = 2).…”

Section: Resultsmentioning

confidence: 99%

Germline Variants in 32 Cancer-Related Genes among 700 Chinese Breast Cancer Patients by Next-Generation Sequencing: A Clinic-Based, Observational Study

Yang

Xie

Liu

et al. 2022

IJMS

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Breast cancer (BC) is associated with hereditary components, and some deleterious germline variants have been regarded as effective therapeutic targets. We conducted a clinic-based, observational study to better understand the distribution of deleterious germline variants and assess any clinicopathological predictors related to the variants among Chinese BC patients using a 32 cancer-related genes next-generation sequencing panel. Between November 2020 and February 2022, a total of 700 BC patients were recruited, and 13.1% (92/700) of them carried deleterious germline variants in 15 cancer-related genes, including 37 (37/700, 5.3%) in BRCA2, 29 (29/700, 4.1%) in BRCA1, 8 (8/700, 1.1%) in PALB2, 4 (4/700, 0.6%) in NBN, 3 (3/700, 0.4%) in MRE11A, 3 (3/700, 0.4%) in TP53 and 12 (12/700, 1.7%) in other genes. There were 28 novel variants detected: 5 in BRCA1, 14 in BRCA2, and 9 in non-BRCA1/2 genes. The variants in panel genes, HRR (homologous recombination repair)-related genes, and BRCA1/2 were significantly associated with the following clinicopathological factors: age at the initial diagnosis of BC, family history of any cancer, molecular subtype, Ki-67 index, and hereditary risk. In conclusion, we further expanded the spectrum of germline deleterious variants in Chinese BC patients, and the clinicopathological predictors of variants were identified to facilitate clinical genetic testing and counseling for appropriate individuals.

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“…In a large-scale cohort with 1,245 pathogenic variants identified, 48 most common pathogenic BRCA1/2 variants (39.86% of total) were not reported as common variants in Caucasians ( 15 ). The pathogenic variant BRCA1 c.5470_5477del was determined as a founder mutation in the Chinese Han population ( 25 , 26 ). Interestingly, another systematic review with 2,128 BRCA1/2 variants derived from 35,178 Chinese individuals from 23 provinces also reported that c.5470_5477del ranked as the highest frequency of all BRCA1 variants identified while the c.3109C>T ranks highest in BRCA2 ( 12 ).…”

Section: Overall Prevalence and Spectrum Of Brca M...mentioning

confidence: 99%

Overview on population screening for carriers with germline BRCA mutation in China

Lei

Zhang²,

Zhang³

et al. 2022

Front. Oncol.

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Carriers with BRCA1/2 germline pathogenic variants are associated with a high risk of breast and ovarian cancers (also pancreatic and prostate cancers). While the spectrum on germline BRCA mutations among the Chinese population shows ethnic specificity, the identification of carriers with germline BRCA mutation before cancer onset is the most effective approach to protect them. This review focused on the current status of BRCA1/2 screening, the surveillance and prevention measures, and discussed the issues and potential impact of BRCA1/2 population screening in China. We conducted literature research on databases PubMed and Google Scholar, as well as Chinese databases CNKI and Wangfang Med Online database (up to 31 March 2022). Latest publications on germline BRCA1/2 prevalence, spectrum, genetic screening as well as carrier counseling, surveillance and prevention were captured where available. While overall 15,256 records were retrieved, 72 publications using germline BRCA1/2 testing were finally retained for further analyses. Germline BRCA1/2 mutations are common in Chinese patients with hereditary breast, ovarian, prostate and pancreatic cancers. Within previous studies, a unique BRCA mutation spectrum in China was revealed. Next-generation sequencing panel was considered as the most common method for BRCA1/2 screening. Regular surveillance and preventive surgeries were tailored to carriers with mutated-BRCA1/2. We recommend that all Chinese diagnosed with breast, ovarian, pancreatic or prostate cancers and also healthy family members, shall undergo BRCA1/2 gene test to provide risk assessment. Subsequently, timely preventive measures for mutation carriers are recommended after authentic genetic counseling.

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Identification of BRCA1:c.5470_5477del as a Founder Mutation in Chinese Ovarian Cancer Patients

Cited by 4 publications

References 32 publications

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

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

Germline Variants in 32 Cancer-Related Genes among 700 Chinese Breast Cancer Patients by Next-Generation Sequencing: A Clinic-Based, Observational Study

Overview on population screening for carriers with germline BRCA mutation in China

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