{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T08:28:24Z","timestamp":1684744104715},"reference-count":28,"publisher":"Korean Cancer Association","issue":"1","license":[{"start":{"date-parts":[[2022,6,8]],"date-time":"2022-06-08T00:00:00Z","timestamp":1654646400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/3.0\/"}],"funder":[{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Health & Welfare","award":["HI17C2206"],"award-info":[{"award-number":["HI17C2206"]}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2016R1A5A1010148"],"award-info":[{"award-number":["2016R1A5A1010148"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["e-crt.org"],"crossmark-restriction":true},"short-container-title":["Cancer Res Treat"],"published-print":{"date-parts":[[2023,1,15]]},"abstract":"Purpose<i>BRCA1<\/i> and <i>BRCA2<\/i> are among the most important genes involved in DNA repair via homologous recombination (HR). Germline <i>BRCA1\/2<\/i> (<i>gBRCA1\/2<\/i>)-related cancers have specific characteristics and treatment options but conducting <i>gBRCA1\/2<\/i> testing and interpreting the genetic imprint are sometimes complicated. Here, we describe the concordance of <i>gBRCA1\/2<\/i> derived from a panel of clinical tumor tissues using next-generation sequencing (NGS) and genetic aspects of tumors harboring <i>gBRCA1\/2<\/i> pathogenic variants.Materials and MethodsTargeted sequencing was performed using available tumor tissue from patients who underwent <i>gBRCA1\/2<\/i> testing. Comparative genomic analysis was performed according to <i>gBRCA1\/2<\/i> pathogenicity.ResultsA total of 321 patients who underwent <i>gBRCA1\/2<\/i> testing were screened, and 26 patients with <i>gBRCA1\/2<\/i> pathogenic (<i>gBRCA1\/2p<\/i>) variants, eight patients with <i>gBRCA1\/2<\/i> variants of uncertain significance (VUS; <i>gBRCA1\/2v<\/i>), and 43 patients with <i>gBRCA1\/2<\/i> wild-type (<i>gBRCA1\/2w<\/i>) were included in analysis. Mutations in <i>TP53<\/i> (49.4%) and <i>PIK3CA<\/i> (23.4%) were frequently detected in all samples. The number of single-nucleotide variants (SNVs) per tumor tissue was higher in the <i>gBRCA1\/2w<\/i> group than that in the <i>gBRCA1\/2p<\/i> group (14.81 vs. 18.86, p=0.278). Tumor mutation burden (TMB) was significantly higher in the <i>gBRCA1\/2w<\/i> group than in the <i>gBRCA1\/2p<\/i> group (10.21 vs. 13.47, p=0.017). Except for <i>BRCA1\/2<\/i>, other HR-related genes were frequently mutated in patients with <i>gBRCA1\/2w<\/i>.ConclusionWe demonstrated high sensitivity of <i>gBRCA1\/2<\/i> in tumors analyzed by NGS using a panel of tumor tissues. TMB value and aberration of non-<i>BRCA1\/2<\/i> HR-related genes differed significantly according to <i>gBRCA1\/2<\/i> pathogenicity in patients with breast cancer.<\/jats:p>","DOI":"10.4143\/crt.2021.1567","type":"journal-article","created":{"date-parts":[[2022,6,8]],"date-time":"2022-06-08T05:25:50Z","timestamp":1654665950000},"page":"155-166","update-policy":"http:\/\/dx.doi.org\/10.4143\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Genomic Signatures from Clinical Tumor Sequencing in Patients with Breast Cancer Having Germline BRCA1\/2 Mutation"],"prefix":"10.4143","volume":"55","author":[{"given":"Ju Won","family":"Kim","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyo Eun","family":"Kang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jimi","family":"Choi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seung Gyu","family":"Yun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seung Pil","family":"Jung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soo Yeon","family":"Bae","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji Young","family":"You","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoon-Ji","family":"Choi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yeul Hong","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyong Hwa","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2954","reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2016.155"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2016.10.013"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1802905"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1706450"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2008.16.6231"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1002\/(sici)1098-2388(200006)18:4<287::aid-ssu3>3.0.co;2-5"},{"key":"ref7","first-page":"e58","volume-title":"Diagnostic screening workflow for mutations in the BRCA1 and BRCA2 genes","author":"Lai","year":"2015"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1200\/po.17.00286"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1101\/gr.183053.114"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaa7161"},{"key":"ref12","first-page":"djv351","volume-title":"Germline findings in tumor-only sequencing: points to consider for clinicians and laboratories","author":"Raymond","year":"2016"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.5483\/bmbrep.2021.54.7.045"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-017-0424-2"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1101\/745265"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1406498"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa1348"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.mct-17-0386"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0312-8"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1038\/s41417-020-0174-y"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2016.34.15_suppl.3057"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.ccr-18-0468"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2021.7728"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.mcr-19-1108"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdz239.019"},{"key":"ref26","volume-title":"Clinical trials.gov identifier: NCT03330847 [Internet]","year":"2017"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.18632\/aging.102783"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.01475"}],"container-title":["Cancer Research and Treatment"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/e-crt.org\/upload\/pdf\/crt-2021-1567.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/e-crt.org\/journal\/view.php?doi=10.4143\/crt.2021.1567","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/e-crt.org\/upload\/pdf\/crt-2021-1567.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,12]],"date-time":"2023-01-12T01:15:04Z","timestamp":1673486104000},"score":1,"resource":{"primary":{"URL":"http:\/\/e-crt.org\/journal\/view.php?doi=10.4143\/crt.2021.1567"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,15]]},"references-count":28,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2023,1]]}},"URL":"https:\/\/doi.org\/10.4143\/crt.2021.1567","relation":{},"ISSN":["1598-2998","2005-9256"],"issn-type":[{"value":"1598-2998","type":"print"},{"value":"2005-9256","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,15]]},"assertion":[{"value":"2021-12-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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