{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T14:04:35Z","timestamp":1780581875417,"version":"3.54.1"},"reference-count":45,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,9,20]],"date-time":"2016-09-20T00:00:00Z","timestamp":1474329600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005010","name":"Italian Association for Cancer Research","doi-asserted-by":"publisher","award":["AIRC\u2010IG16933"],"award-info":[{"award-number":["AIRC\u2010IG16933"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005010","name":"Italian Association for Cancer Research","doi-asserted-by":"publisher","award":["AIRC\u2010IG12821"],"award-info":[{"award-number":["AIRC\u2010IG12821"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005010","name":"Italian Association for Cancer Research","doi-asserted-by":"publisher","award":["AIRC\u2010IG15547"],"award-info":[{"award-number":["AIRC\u2010IG15547"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["Institutional Strategic Projects 5\u2009\u00d7\u20091000"],"award-info":[{"award-number":["Institutional Strategic Projects 5\u2009\u00d7\u20091000"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2017,1,15]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Male breast cancer (MBC) is a rare disease whose etiology appears to be largely associated with genetic factors. <jats:italic>BRCA1<\/jats:italic> and <jats:italic>BRCA2<\/jats:italic> mutations account for about 10% of all MBC cases. Thus, a fraction of MBC cases are expected to be due to genetic factors not yet identified. To further explain the genetic susceptibility for MBC, whole\u2010exome sequencing (WES) and targeted gene sequencing were applied to high\u2010risk, <jats:italic>BRCA1\/2<\/jats:italic> mutation\u2013negative MBC cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Germ\u2010line DNA of 1 male and 2 female <jats:italic>BRCA1\/2<\/jats:italic> mutation\u2013negative breast cancer (BC) cases from a pedigree showing a first\u2010degree family history of MBC was analyzed with WES. Targeted gene sequencing for the validation of WES results was performed for 48 high\u2010risk, <jats:italic>BRCA1\/2<\/jats:italic> mutation\u2013negative MBC cases from an Italian multicenter study of MBC. A case\u2010control series of 433 <jats:italic>BRCA1\/2<\/jats:italic> mutation\u2013negative MBC and female breast cancer (FBC) cases and 849 male and female controls was included in the study.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>WES in the family identified the partner and localizer of BRCA2 (<jats:italic>PALB2<\/jats:italic>) c.419delA truncating mutation carried by the proband, her father, and her paternal uncle (all affected with BC) and the <jats:italic>N<\/jats:italic>\u2010acetyltransferase 1 (<jats:italic>NAT1<\/jats:italic>) c.97C&gt;T nonsense mutation carried by the proband's maternal aunt. Targeted <jats:italic>PALB2<\/jats:italic> sequencing detected the c.1984A&gt;T nonsense mutation in 1 of the 48 <jats:italic>BRCA1\/2<\/jats:italic> mutation\u2013negative MBC cases. <jats:italic>NAT1<\/jats:italic> c.97C&gt;T was not found in the case\u2010control series.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>These results add strength to the evidence showing that <jats:italic>PALB2<\/jats:italic> is involved in BC risk for both sexes and indicate that consideration should be given to clinical testing of <jats:italic>PALB2<\/jats:italic> for <jats:italic>BRCA1\/2<\/jats:italic> mutation\u2013negative families with multiple MBC and FBC cases. <jats:bold><jats:italic>Cancer<\/jats:italic> 2017;123:210\u2013218.<\/jats:bold> \u00a9 <jats:italic>2016 American Cancer Society<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.30337","type":"journal-article","created":{"date-parts":[[2016,9,20]],"date-time":"2016-09-20T13:43:08Z","timestamp":1474378988000},"page":"210-218","source":"Crossref","is-referenced-by-count":35,"title":["Whole\u2010exome sequencing and targeted gene sequencing provide insights into the role of <i>PALB2<\/i> as a male breast cancer susceptibility gene"],"prefix":"10.1002","volume":"123","author":[{"given":"Valentina","family":"Silvestri","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine Sapienza University of Rome Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Zelli","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine Sapienza University of Rome Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia","family":"Valentini","sequence":"additional","affiliation":[{"name":"Department of 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Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Oliani","sequence":"additional","affiliation":[{"name":"Oncology Unit, Local Health and Social Care Unit ULSS5 Ovest Vicentino Montecchio Maggiore Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Barana","sequence":"additional","affiliation":[{"name":"Oncology Unit, Local Health and Social Care Unit ULSS5 Ovest Vicentino Montecchio Maggiore Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Castrignan\u00f2","sequence":"additional","affiliation":[{"name":"Supercomputing Applications and Innovation Department Interuniversity Consortium for Super Computing CINECA Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Viel","sequence":"additional","affiliation":[{"name":"Unit of Functional Onco\u2010Genomics and Genetics, Aviano Oncology Reference Center CRO, National Cancer 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