{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T12:09:14Z","timestamp":1764331754012},"reference-count":23,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2008,2,26]],"date-time":"2008-02-26T00:00:00Z","timestamp":1203984000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2008,4]]},"abstract":"<jats:p>While there are many reports in the literature of mutation testing of <jats:italic>BRCA1<\/jats:italic> and <jats:italic>BRCA2<\/jats:italic> in breast\/ovarian cancer families, the question of which type of ovarian cancers are relevant still pertains. We have undertaken whole gene screening including multiple ligation\u2010dependent probe amplification in an affected individual within 442 unrelated non\u2010Jewish families containing at least one reported ovarian cancer diagnosed less than 50 years or at any age with family history of breast or ovarian cancer for mutations in <jats:italic>BRCA1<\/jats:italic> and <jats:italic>BRCA2.<\/jats:italic> A total of 166 mutations were identified 110 (25%) in <jats:italic>BRCA1<\/jats:italic> and 56 (13%) in <jats:italic>BRCA2<\/jats:italic>. In families without confirmation of ovarian diagnosis, the detection rate drops significantly. In families fulfilling Breast Cancer Linkage Consortium (BCLC) criteria with confirmed ovarian cancer cases, the mutation detection frequency was 80%. If only BCLC families with unconfirmed ovarian cancers were included, the detection rate dropped to 36% when a relevant ovarian cancer diagnosis was not confirmed. In BCLC families containing only one ovarian cancer, <jats:italic>BRCA2<\/jats:italic> accounted for 45% of identified mutations. No mutations were identified in affected individuals with borderline or mucinous tumours. Detection rates dropped below the 10\/20% international thresholds in a number of families with unconfirmed ovarian cancers. Borderline\/mucinous pathology substantially reduces the likelihood of identifying a BRCA1\/2 mutation. Strenuous efforts should be made to confirm ovarian pathology if the lack of confirmation or refuting the diagnosis would decrease a family\u2019s likelihood of mutation detection below screening thresholds. In the UK, a higher proportion of families harbour <jats:italic>BRCA2<\/jats:italic> pathogenic mutations than predicted from previous studies.<\/jats:p>","DOI":"10.1111\/j.1399-0004.2008.00974.x","type":"journal-article","created":{"date-parts":[[2009,1,23]],"date-time":"2009-01-23T09:30:53Z","timestamp":1232703053000},"page":"338-345","source":"Crossref","is-referenced-by-count":37,"title":["Probability of <i>BRCA1\/2<\/i> mutation varies with ovarian histology: results from screening 442 ovarian cancer families"],"prefix":"10.1111","volume":"73","author":[{"given":"DGR","family":"Evans","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Young","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Bulman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Shenton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Wallace","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F","family":"Lalloo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2008,2,26]]},"reference":[{"key":"e_1_2_5_2_2","unstructured":"Cancer Research UK. 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