{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T20:32:55Z","timestamp":1782937975828,"version":"3.54.5"},"reference-count":27,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,11,8]],"date-time":"2021-11-08T00:00:00Z","timestamp":1636329600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BJOG"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To determine the frequency of germline and somatic pathogenic <jats:italic>BRCA1<\/jats:italic> and <jats:italic>BRCA2<\/jats:italic> variants in patients with high\u2010grade serous ovarian cancer tested by next\u2010generation sequencing (NGS), with the aim of defining the best strategy to be implemented in future routine testing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>National retrospective audit.<\/jats:p><\/jats:sec><jats:sec><jats:title>Setting<\/jats:title><jats:p>The All Wales Medical Genomics Service (AWMGS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Population<\/jats:title><jats:p>Patients with high\u2010grade serous ovarian\/fallopian tube\/peritoneal cancer referred by oncologists to the AWMGS between February 2015 and February 2021 for germline and\/or tumour testing of the <jats:italic>BRCA1<\/jats:italic> and <jats:italic>BRCA2<\/jats:italic> genes by NGS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Analysis of NGS data from germline and\/or tumour testing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Main outcome measures<\/jats:title><jats:p>Frequency of <jats:italic>BRCA1<\/jats:italic> and <jats:italic>BRCA2<\/jats:italic> pathogenic variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The overall observed germline\/somatic pathogenic variant detection rate was 11.6% in the 844 patients included in this study, with a 9.2% (73\/791) germline pathogenic variant detection rate. Parallel tumour and germline testing was carried out for 169 patients and the overall pathogenic variant detection rate for this cohort was 14.8%, with 6.5% (11\/169) shown to have a somatic pathogenic variant. Two <jats:italic>BRCA1<\/jats:italic> dosage variants were found during germline screens, representing 2.0% (2\/98) of patients with a pathogenic variant that would have been missed through tumour testing alone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Parallel germline and tumour <jats:italic>BRCA1<\/jats:italic> and <jats:italic>BRCA2<\/jats:italic> testing maximises the detection of pathogenic variants in patients with high\u2010grade serous ovarian cancer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Tweetable abstract<\/jats:title><jats:p>Parallel germline and tumour testing maximises <jats:italic>BRCA<\/jats:italic> pathogenic variant detection in ovarian cancer.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1471-0528.16975","type":"journal-article","created":{"date-parts":[[2021,10,19]],"date-time":"2021-10-19T17:23:28Z","timestamp":1634664208000},"page":"433-442","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["The detection of germline and somatic <i>BRCA1\/2<\/i> genetic variants through parallel testing of patients with high\u2010grade serous ovarian cancer: a national retrospective audit"],"prefix":"10.1111","volume":"129","author":[{"given":"B","family":"Frugtniet","sequence":"first","affiliation":[{"name":"All Wales Medical Genomics Laboratory University Hospital of Wales Cardiff UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Morgan","sequence":"additional","affiliation":[{"name":"All Wales Medical Genomics Laboratory University Hospital of Wales Cardiff UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Murray","sequence":"additional","affiliation":[{"name":"All Wales Medical Genomics Service University Hospital of Wales Cardiff UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Palmer\u2010Smith","sequence":"additional","affiliation":[{"name":"All Wales Medical Genomics Laboratory University Hospital of Wales Cardiff UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"White","sequence":"additional","affiliation":[{"name":"All Wales Medical Genomics Laboratory University Hospital of Wales Cardiff UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Jones","sequence":"additional","affiliation":[{"name":"South West Wales Cancer Centre Singleton Hospital Swansea UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Hanna","sequence":"additional","affiliation":[{"name":"Velindre Cancer Centre Velindre University NHS Trust Cardiff UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Fuller","sequence":"additional","affiliation":[{"name":"Bwrdd Iechyd Prifysgol Betsi Cadwaladr University Health Board Bangor UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Hudson","sequence":"additional","affiliation":[{"name":"Velindre Cancer Centre Velindre University NHS Trust Cardiff UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Mullard","sequence":"additional","affiliation":[{"name":"Bwrdd Iechyd Prifysgol Betsi Cadwaladr University Health Board Bangor UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"AE","family":"Quinton","sequence":"additional","affiliation":[{"name":"Velindre Cancer Centre Velindre University NHS Trust Cardiff UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,11,8]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1911361"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(14)70228-1"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2017.08.022"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1810858"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)32440-6"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-020-06948-5"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2017.7112"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers10020057"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/1471-0528.15171"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2017-105140"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-60149-5"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep29506"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2016-103902"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-020-0692-y"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.748"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-020-6693-y"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.01318"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/01443615.2020.1820466"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/ijgc-2020-002112"},{"key":"e_1_2_5_21_1","first-page":"1","article-title":"ACGS best practice guidelines for variant classification in rare disease 2020","author":"Ellard S","year":"2020","journal-title":"Assoc Clin Genomic Sci (ACGS)"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2019-106759"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.39.8545"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1086\/302974"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.02960"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2020.03.283"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41523-020-00174-9"}],"container-title":["BJOG: An International Journal of Obstetrics &amp; Gynaecology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1471-0528.16975","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/1471-0528.16975","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1471-0528.16975","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T02:28:48Z","timestamp":1692498528000},"score":1,"resource":{"primary":{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/10.1111\/1471-0528.16975"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,8]]},"references-count":27,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022,2]]}},"alternative-id":["10.1111\/1471-0528.16975"],"URL":"https:\/\/doi.org\/10.1111\/1471-0528.16975","archive":["Portico"],"relation":{},"ISSN":["1470-0328","1471-0528"],"issn-type":[{"value":"1470-0328","type":"print"},{"value":"1471-0528","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,8]]},"assertion":[{"value":"2021-03-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-09-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}