{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T11:59:20Z","timestamp":1791460760402,"version":"4.3.4"},"reference-count":52,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,9,3]],"date-time":"2014-09-03T00:00:00Z","timestamp":1409702400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100001006","name":"Breast Cancer Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001006","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Next\u2010generation sequencing (NGS) allows for simultaneous sequencing of multiple cancer susceptibility genes and, for an individual, may be more efficient and less expensive than sequential testing. The authors assessed the frequency of deleterious germline mutations among individuals with breast cancer who were referred for <jats:italic>BRCA1<\/jats:italic> and <jats:italic>BRCA2<\/jats:italic> (<jats:italic>BRCA1\/2<\/jats:italic>) gene testing using a panel of 25 genes associated with inherited cancer predisposition.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>This was a cross\u2010sectional study using NGS in 2158 individuals, including 1781 who were referred for commercial <jats:italic>BRCA1\/2<\/jats:italic> gene testing (cohort 1) and 377 who had detailed personal and family history and had previously tested negative for <jats:italic>BRCA1\/2<\/jats:italic> mutations (cohort 2).<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Mutations were identified in 16 genes, most frequently in <jats:italic>BRCA1<\/jats:italic>, <jats:italic>BRCA2<\/jats:italic>, <jats:italic>CHEK2<\/jats:italic>, <jats:italic>ATM<\/jats:italic>, and <jats:italic>PALB2<\/jats:italic>. Among the participants in cohort 1, 9.3% carried a <jats:italic>BRCA1\/2<\/jats:italic> mutation, 3.9% carried a mutation in another breast\/ovarian cancer susceptibility gene, and 0.3% carried an incidental mutation in another cancer susceptibility gene unrelated to breast or ovarian cancer. In cohort 2, the frequency of mutations in breast\/ovarian\u2010associated genes other than <jats:italic>BRCA1\/2<\/jats:italic> was 2.9%, and an additional 0.8% had an incidental mutation. In cohort 1, Lynch syndrome\u2010related mutations were identified in 7 individuals. In contrast to <jats:italic>BRCA1\/2<\/jats:italic> mutations, neither age at breast cancer diagnosis nor family history of ovarian or young breast cancer predicted for other mutations. The frequency of mutations in genes other than <jats:italic>BRCA1\/2<\/jats:italic> was lower in Ashkenazi Jews compared with non\u2010Ashkenazi individuals (<jats:italic>P<\/jats:italic>=.026).<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Using an NGS 25\u2010gene panel, the frequency of mutations in genes other than <jats:italic>BRCA1\/2<\/jats:italic> was 4.3%, and most mutations (3.9%) were identified in genes associated with breast\/ovarian cancer. <jats:bold><jats:italic>Cancer<\/jats:italic> 2015;121:25\u201333<\/jats:bold>. \u00a9 <jats:italic>2014 American Cancer Society<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.29010","type":"journal-article","created":{"date-parts":[[2014,9,3]],"date-time":"2014-09-03T10:44:16Z","timestamp":1409741056000},"page":"25-33","source":"Crossref","is-referenced-by-count":383,"title":["Frequency of mutations in individuals with breast cancer referred for <scp><i>BRCA<\/i><\/scp><i>1<\/i> and <scp><i>BRCA<\/i><\/scp><i>2<\/i> testing using next\u2010generation sequencing with a 25\u2010gene panel"],"prefix":"10.1002","volume":"121","author":[{"given":"Nadine","family":"Tung","sequence":"first","affiliation":[{"name":"Division of Hematology\u2010Oncology Beth Israel Deaconess Medical Center Boston Massachusetts"},{"name":"Department of Medicine Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Battelli","sequence":"additional","affiliation":[{"name":"Division of Hematology\u2010Oncology Beth Israel Deaconess Medical Center Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Allen","sequence":"additional","affiliation":[{"name":"Clinical Affairs Myriad Genetic Laboratories, Inc. Salt Lake City Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajesh","family":"Kaldate","sequence":"additional","affiliation":[{"name":"Clinical Affairs Myriad Genetic Laboratories, Inc. Salt Lake City Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satish","family":"Bhatnagar","sequence":"additional","affiliation":[{"name":"Technical and Product Development Myriad Genetics, Inc. Salt Lake City Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karla","family":"Bowles","sequence":"additional","affiliation":[{"name":"Diagnostic Development Myriad Genetic Laboratories, Inc. Salt Lake City Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten","family":"Timms","sequence":"additional","affiliation":[{"name":"Research Myriad Genetics, Inc. Salt Lake City Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judy E.","family":"Garber","sequence":"additional","affiliation":[{"name":"Department of Medicine Harvard Medical School Boston Massachusetts"},{"name":"Division of Population Sciences and Adult Oncology Dana\u2010Farber Cancer Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Herold","sequence":"additional","affiliation":[{"name":"Division of Hematology\u2010Oncology Beth Israel Deaconess Medical Center Boston Massachusetts"},{"name":"Department of Medicine Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leif","family":"Ellisen","sequence":"additional","affiliation":[{"name":"Department of Medicine Harvard Medical School Boston Massachusetts"},{"name":"Department of Hematology\/Oncology and Medicine Massachusetts General Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill","family":"Krejdovsky","sequence":"additional","affiliation":[{"name":"Cancer Genetics and Prevention Program Beth Israel Deaconess Medical Center Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"DeLeonardis","sequence":"additional","affiliation":[{"name":"Cancer Genetics and Prevention Program Beth Israel Deaconess Medical Center Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Sedgwick","sequence":"additional","affiliation":[{"name":"Cancer Genetics and Prevention Program Beth Israel Deaconess Medical Center Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Soltis","sequence":"additional","affiliation":[{"name":"Cancer Genetics and Prevention Program Beth Israel Deaconess Medical Center Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Roa","sequence":"additional","affiliation":[{"name":"Diagnostic Development Myriad Genetic Laboratories, Inc. Salt Lake City Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Wenstrup","sequence":"additional","affiliation":[{"name":"Medical Services Myriad Genetic Laboratories, Inc. Salt Lake City Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne\u2010Renee","family":"Hartman","sequence":"additional","affiliation":[{"name":"Clinical Affairs Myriad Genetic Laboratories, Inc. Salt Lake City Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,9,3]]},"reference":[{"key":"e_1_2_7_2_1","unstructured":"National Cancer Institute. SEER Cancer Statistics Factsheets: Breast Cancer. Bethesda MD: National Cancer Institute;2014. Available at:http:\/\/seer.cancer.gov\/statfacts\/html\/breast.html. 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