<i>BRCA1/2</i>mutation status in patients with metachronous breast and ovarian malignancies: clues towards the implementation of genetic counseling

Chao, Angel; Lin, Yun-Hsuan; Yang, Lan-Yan; Wu, Ren‐Chin; Chang, W. Y.; Chang, Pi Yueh; Chang, Shih Cheng; Lin, Chia-Yang; Huang, Hsuan-Rong; Lin, Cheng Tao; Chou, Hung Hsueh; Huang, Kuo‐Lun; Kuo, Wen-Ling; Chang, Ting Chang; Lai, Cheng‐Hung

doi:10.3802/jgo.2020.31.e24

Cited by 5 publications

(6 citation statements)

References 31 publications

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“…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 ]. BRCA2 c.2339C > G has been detected in Taiwanese [ 67 ], and Japanese [ 68 ] individuals.…”

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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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%

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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“…Studies were selected by the following inclusion criteria: 1) cancer patients should be pathologically confirmed, 2) germline variants in BRCA1/2 should be genotyped, and 3) studies on nonhuman or cell line were excluded. Thoroughly searching PubMed and Google Scholar using the keywords such as “ BRCA1 ” “ BRCA2 ” “Taiwan” “Taiwanese” and “cancer predisposition” we identified 15 publications reporting the BRCA data from Taiwanese cancer patients between 1997 and 2020 ( Liu et al, 1997 ; Li et al, 1999 ; Wang et al, 2000 ; Chen et al, 2003 ; Lin et al, 2003 ; Chen et al, 2005 ; Chang et al, 2006 ; Kuo et al, 2012 ; Chao et al, 2016 ; Lin et al, 2016 ; Sung et al, 2017 ; Wang et al, 2018 ; Lin et al, 2019 ; Chao et al, 2020 ; Lin et al, 2020 ). Searching Taiwan Biobank ( https://taiwanview.twbiobank.org.tw/index ; accessed December 15, 2020) using the keywords “ BRCA1 ” and “ BRCA2 ” we obtained the BRCA variation data derived from Taiwanese general population.…”

Section: Methodsmentioning

confidence: 99%

BRCA1 and BRCA2 Variation in Taiwanese General Population and the Cancer Cohort

Chian¹,

Sinha²,

Qin³

et al. 2021

Front. Mol. Biosci.

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BRCA1 and BRCA2 (BRCA) play essential roles in maintaining genome stability. Rapidly evolving human BRCA generates oncogenic variants causing high cancer risk. BRCA variation is ethnic-specific in reflecting adaptation and/or effects of genetic drift. Taiwanese population of 23.8 million is an admixture of multiple ethnic origins; Taiwan’s subtropical and tropical climate and geographically islandic location provide a unique natural environment. Therefore, Taiwanese population provides a unique model to study human BRCA variation. Through collecting, standardizing, annotating, and classifying publicly available BRCA variants derived from Taiwanese general population and the cancer cohort, we identified 335 BRCA variants, of which 164 were from 1,517 non-cancer individuals, 126 from 2,665 cancer individuals, and 45 from both types of individuals. We compared the variant data with those from other ethnic populations such as mainland Chinese, Macau Chinese, Japanese, Korean, Indian, and non-Asians. We observed that the sharing rates with other Asian ethnic populations were correlated with its genetic relationship. Over 60% of the 335 Taiwanese BRCA variants were VUS, unclassified variants, or novel variants, reflecting the ethnic-specific features of Taiwanese BRCA variation. While it remains challenging to classify these variants, our structural and in silico analyses predicted their enrichment of BRCA deleterious variants. We further determined the 3.8% prevalence of BRCA pathogenic variants in the Taiwanese breast cancer cohort, and determined 0.53% prevalence of the BRCA pathogenic variants in Taiwanese general population, with the estimated 126,140 BRCA pathogenic variant carriers. We identified BRCA2 c.5164_5165delAG at BRCA2 BRC6 motif as a potential founder mutation in Taiwanese population. Our study on BRCA variation in Taiwanese and other East Asian populations demonstrates that ethnic specificity is a common phenomenon for BRCA variation in East Asian population; the data generated from the study provide a reference for clinical applications in BRCA-related cancer in Taiwanese population.

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“…A high proportion of mutations were in BRCA1/2 genes, they were identified in 10% of OV cancer patients and 35.5% of BROV cancer patients. A high BRCA1/2 mutation rate of 38.9% has also been demonstrated in Taiwan in a cohort of 18 synchronous/metachronous BROV cancer studies (Chao et al, 2020 ). BRCA1/2 mutations (14.6%–22.8%) were more likely found in high‐grade serous carcinoma of ovarian than other types of ovarian cancer (Alsop et al, 2012 ; Candido‐dos‐Reis et al, 2015 ; Harter et al, 2016 ).…”

Section: Discussionmentioning

confidence: 79%

“…Mutations in BRCA1/2 genes were detected in approximately 12%–25% of patients with high‐grade serous ovarian carcinoma (HGSC) (Chao et al, 2016 ; Sakamoto et al, 2016 ; Walsh et al, 2011 ) while the prevalence of BRCA1/2 mutation was (3.7%–4.7%) in women with breast cancer, aged between 40 and 59 years (Buys et al, 2017 ). The BRCA1/2 mutation rate in 18 Chinese cohorts with metachronous BROV malignancies was as high as 38.9% (Chao et al, 2020 ). There were well‐established counseling strategies and management guidelines for early intervention or prevention through increased surveillance, such as clinical breast examination every 6–12 months and addition of annual breast MRI, mammography at age 25, and consideration of risk‐reducing interventions including chemoprevention and prophylactic mastectomy or salpingo‐oophorectomy (Petrucelli et al, 1998 ; Smith, 2012 ).…”

Section: Introductionmentioning

confidence: 99%

Germline mutations in Chinese ovarian cancer with or without breast cancer

Kwong

Shin

et al. 2022

Molec Gen & Gen Med

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Background Ovarian and breast cancers are known to have significant genetic components. Considering the differences in the mutation spectrum across ethnicity, it is important to identify hereditary breast and ovarian cancer (HBOC) genes mutation in Chinese for clinical management. Methods Two cohorts of 451 patients with ovarian cancer only (OV) and 93 patients with both breast and ovarian (BROV) cancers were initially screened for BRCA1, BRCA2, TP53, and PTEN. 109 OV and 43 BROV patients with extensive clinical risk and were being tested negative, were then further characterized by 30‐gene panel analysis. Results Pathogenic BRCA1/2 variants were identified in 45 OV patients and 33 BROV patients, giving a prevalence of 10% and 35.5%, respectively. After the extended screening, mutations in other HBOC genes were identified in an additional 12.8% (14/109) of the OV cohort and 14% (6/43) in the BROV cohort. The most commonly mutated genes in the OV cohort were MSH2 (4.6%) while in the BROV cohort were MSH2 (4.7%) and PALB2 (4.7%). With this extended multigene testing strategy, pathogenic mutations were detected in 12.8% of OV patients (BRCAs: 10%; additional genes: 12.8%) and 40.9% (BRCAs: 35.5%; additional genes: 14%) of BROV patients. Conclusion Extended characterization of the contributions of HBOC genes to OV and BROV patients has significant impacts on further management in patients and their families, expanding the screening net for more asymptomatic individuals.

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BRCA1/2mutation status in patients with metachronous breast and ovarian malignancies: clues towards the implementation of genetic counseling

Cited by 5 publications

References 31 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

BRCA1 and BRCA2 Variation in Taiwanese General Population and the Cancer Cohort

Germline mutations in Chinese ovarian cancer with or without breast cancer

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