{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T16:39:22Z","timestamp":1790354362697,"version":"4.1.0"},"reference-count":4,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,1,18]],"date-time":"2021-01-18T00:00:00Z","timestamp":1610928000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,1,18]],"date-time":"2021-01-18T00:00:00Z","timestamp":1610928000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81772802"],"award-info":[{"award-number":["81772802"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82073269"],"award-info":[{"award-number":["82073269"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shanghai science and technology innovation action plan of China","award":["17JC1404400"],"award-info":[{"award-number":["17JC1404400"]}]},{"name":"Shanghai science and technology innovation action plan of China","award":["16DZ19102"],"award-info":[{"award-number":["16DZ19102"]}]},{"name":"Special Funds for Technological Innovation of Shanghai Jiao Tong University","award":["YG2016MS22"],"award-info":[{"award-number":["YG2016MS22"]}]},{"DOI":"10.13039\/501100018537","name":"National Science and Technology Major Project","doi-asserted-by":"crossref","award":["2019ZX09301-158"],"award-info":[{"award-number":["2019ZX09301-158"]}],"id":[{"id":"10.13039\/501100018537","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Chinese Academy of Science","award":["XDA12020223"],"award-info":[{"award-number":["XDA12020223"]}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LZ16H160002"],"award-info":[{"award-number":["LZ16H160002"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013115","name":"Zhejiang Provincial Program for the Cultivation of High-Level Innovative Health Talents","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013115","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018537","name":"National Science and Technology Major Project","doi-asserted-by":"crossref","award":["2019ZX09301-158"],"award-info":[{"award-number":["2019ZX09301-158"]}],"id":[{"id":"10.13039\/501100018537","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Hematol Oncol"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Accurate interpretation of <jats:italic>BRCA1\/2<\/jats:italic> variants is critical for risk assessment and precise treatment of breast cancer (BC). Hence, the establishment of an ethnicity-based <jats:italic>BRCA1\/2<\/jats:italic> variant database of the Chinese population is of paramount importance. In this study, panel-based sequencing served to detect <jats:italic>BRCA1\/<\/jats:italic>2 variants in a Chinese multicenter cohort of 21,216 BC patients and 6434 healthy controls.\n Overall, the percentage of subjects carrying pathogenic variants was 5.5% (1174\/21,216) in BC patients and 1.1% (71\/6434) in healthy controls. We identified 13 pathogenic variants as high-frequency variants that had a frequency of\u2009&gt;\u20090.45\u2030 in BC patients (\u2265\u200910 in 21,216 patients), none of which has been reported in Caucasians. Pathogenic <jats:italic>BRCA1\/2<\/jats:italic> variants correlated with younger onset age, higher frequencies of bilateral and triple-negative BC (TNBC), invasive carcinomas, high histological grades, and family history of BC and other cancers.\n Furthermore, the percentage of the subjects carrying VUS was 9.8% (2071\/21,216) in BC patients and 6.9% (446\/6434) in healthy controls. Based on our cohort study, we unambiguously reclassified 7 out of the 858 VUS resulting in lower VUS ratio in patients (from 9.8 to 7.9%) as well as in healthy control (from 6.9 to 5.3%). We also re-analyzed the 100 variants in 13 exons (2\u20135 and 15\u201323) of the <jats:italic>BRCA1<\/jats:italic> genes using a functional assay (saturation genome editing; SGE). 55 of the 59 VUS had distinct status in the SGE study: 24 (43.6%) were pathogenic, and 31 (56.4%) were benign. Strong ethnicity-specific occurrences of pathogenic <jats:italic>BRCA1\/2<\/jats:italic> variants were identified in the Chinese population. Hence, the findings provide rationale and sequencing information for the implementation of <jats:italic>BRCA1\/2<\/jats:italic> variants tailored to the Chinese population into clinical risk assessment.<\/jats:p>","DOI":"10.1186\/s13045-020-01010-0","type":"journal-article","created":{"date-parts":[[2021,1,18]],"date-time":"2021-01-18T13:04:42Z","timestamp":1610975082000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Prevalence and reclassification of BRCA1 and BRCA2 variants in a large, unselected Chinese Han breast cancer cohort"],"prefix":"10.1186","volume":"14","author":[{"given":"Yun","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honglian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjian","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhigang","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghua","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoling","family":"Weng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiancheng","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijun","family":"Di","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Gires","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongtao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiding","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3481-6940","authenticated-orcid":false,"given":"Hongxia","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,18]]},"reference":[{"issue":"20","key":"1010_CR1","doi-asserted-by":"publisher","first-page":"6113","DOI":"10.1158\/1078-0432.CCR-16-3227","volume":"23","author":"J Sun","year":"2017","unstructured":"Sun J, Meng H, Yao L, Lv M, Bai J, Zhang J, et al. Germline mutations in cancer susceptibility genes in a large series of unselected breast cancer patients. Clin Cancer Res. 2017;23(20):6113\u20139.","journal-title":"Clin Cancer Res"},{"issue":"1","key":"1010_CR2","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1007\/s10549-015-3377-4","volume":"151","author":"E Kang","year":"2015","unstructured":"Kang E, Seong MW, Park SK, Lee JW, Lee J, Kim LS, et al. The prevalence and spectrum of BRCA1 and BRCA2 mutations in Korean population: recent update of the Korean Hereditary Breast Cancer (KOHBRA) study. Breast Cancer Res Treat. 2015;151(1):157\u201368.","journal-title":"Breast Cancer Res Treat"},{"issue":"4","key":"1010_CR3","doi-asserted-by":"publisher","first-page":"962","DOI":"10.1002\/ijc.32176","volume":"145","author":"SP Bhaskaran","year":"2019","unstructured":"Bhaskaran SP, Chandratre K, Gupta H, Zhang L, Wang X, Cui J, et al. Germline variation in BRCA1\/2 is highly ethnic-specific: evidence from over 30,000 Chinese hereditary breast and ovarian cancer patients. Int J Cancer. 2019;145(4):962\u201373.","journal-title":"Int J Cancer"},{"issue":"7726","key":"1010_CR4","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1038\/s41586-018-0461-z","volume":"562","author":"GM Findlay","year":"2018","unstructured":"Findlay GM, Daza RM, Martin B, Zhang MD, Leith AP, Gasperini M, et al. Accurate classification of BRCA1 variants with saturation genome editing. Nature. 2018;562(7726):217\u201322.","journal-title":"Nature"}],"container-title":["Journal of Hematology &amp; Oncology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13045-020-01010-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13045-020-01010-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13045-020-01010-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,18]],"date-time":"2021-01-18T13:25:45Z","timestamp":1610976345000},"score":1,"resource":{"primary":{"URL":"https:\/\/jhoonline.biomedcentral.com\/articles\/10.1186\/s13045-020-01010-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,18]]},"references-count":4,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["1010"],"URL":"https:\/\/doi.org\/10.1186\/s13045-020-01010-0","relation":{},"ISSN":["1756-8722"],"issn-type":[{"value":"1756-8722","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,18]]},"assertion":[{"value":"20 October 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 November 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 January 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The study was approved by the Ethics Committee of all the hospitals involved and was performed according to the Declaration of Helsinki Principles.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"18"}}