{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T10:43:05Z","timestamp":1790764985270,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2019,1,11]],"date-time":"2019-01-11T00:00:00Z","timestamp":1547164800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"The Claudia-von-Schilling foundation Hannover, Germany"},{"name":"MD\/PhD program molecular medicine, The Hannover Biomedical Research School"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:p>NGS\u2010based multiple gene panel resequencing in combination with a high resolution CGH\u2010array was used to identify genetic risk factors for hereditary breast and\/or ovarian cancer in 237 high risk patients who were previously tested negative for pathogenic <jats:italic>BRCA1\/2<\/jats:italic> variants. All patients were screened for pathogenic variants in 94 different cancer predisposing genes. We identified 32 pathogenic variants in 14 different genes (<jats:italic>ATM, BLM, BRCA1, CDH1, CHEK2, FANCG, FANCM, FH, HRAS, PALB2, PMS2, PTEN, RAD51C<\/jats:italic> and <jats:italic>NBN<\/jats:italic>) in 30 patients (12.7%). Two pathogenic <jats:italic>BRCA1<\/jats:italic> variants that were previously undetected due to less comprehensive and sensitive methods were found. Five pathogenic variants are novel, three of which occur in genes yet unrelated to hereditary breast and\/or ovarian cancer (<jats:italic>FANCG, FH<\/jats:italic> and <jats:italic>HRAS<\/jats:italic>). In our cohort we discovered a remarkably high frequency of truncating variants in <jats:italic>FANCM<\/jats:italic> (2.1%), which has recently been suggested as a susceptibility gene for hereditary breast cancer. Two patients of our cohort carried two different pathogenic variants each and 10 other patients in whom a pathogenic variant was confirmed also harbored a variant of unknown significance in a breast and ovarian cancer susceptibility gene. We were able to identify pathogenic variants predisposing for tumor formation in 12.3% of <jats:italic>BRCA1\/2<\/jats:italic> negative breast and\/or ovarian cancer patients.<\/jats:p>","DOI":"10.1002\/ijc.31992","type":"journal-article","created":{"date-parts":[[2018,11,14]],"date-time":"2018-11-14T06:29:40Z","timestamp":1542176980000},"page":"2683-2694","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["The identification of pathogenic variants in <i>BRCA1\/2<\/i> negative, high risk, hereditary breast and\/or ovarian cancer patients: High frequency of <i>FANCM<\/i> pathogenic variants"],"prefix":"10.1002","volume":"144","author":[{"given":"Stephanie","family":"Schubert","sequence":"first","affiliation":[{"name":"Department of Human Genetics Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana L.","family":"van 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