{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T01:42:53Z","timestamp":1789954973948,"version":"4.0.1"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,9,23]],"date-time":"2016-09-23T00:00:00Z","timestamp":1474588800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:p>Breast and ovarian cancer (BC\/OC) predisposition has been attributed to a number of high\u2010 and moderate to low\u2010penetrance susceptibility genes. With the advent of next generation sequencing (NGS) simultaneous testing of these genes has become feasible. In this monocentric study, we report results of panel\u2010based screening of 14 BC\/OC susceptibility genes (<jats:italic>BRCA1, BRCA2, RAD51C, RAD51D, CHEK2, PALB2, ATM, NBN, CDH1, TP53, MLH1, MSH2, MSH6 and PMS2<\/jats:italic>) in a group of 581 consecutive individuals from a German population with BC and\/or OC fulfilling diagnostic criteria for <jats:italic>BRCA1<\/jats:italic> and <jats:italic>BRCA2<\/jats:italic> testing including 179 with a triple\u2010negative tumor. Altogether we identified 106 deleterious mutations in 105 (18%) patients in 10 different genes, including seven different exon deletions. Of these 106 mutations, 16 (15%) were novel and only six were found in <jats:italic>BRCA1\/2<\/jats:italic>. To further characterize mutations located in or nearby splicing consensus sites we performed RT\u2010PCR analysis which allowed confirmation of pathogenicity in 7 of 9 mutations analyzed. In <jats:italic>PALB2<\/jats:italic>, we identified a deleterious variant in six cases. All but one were associated with early onset BC and a positive family history indicating that penetrance for <jats:italic>PALB2<\/jats:italic> mutations is comparable to <jats:italic>BRCA2<\/jats:italic>. Overall, extended testing beyond <jats:italic>BRCA1\/2<\/jats:italic> identified a deleterious mutation in further 6% of patients. As a downside, 89 variants of uncertain significance were identified highlighting the need for comprehensive variant databases. In conclusion, panel testing yields more accurate information on genetic cancer risk than assessing <jats:italic>BRCA1\/2<\/jats:italic> alone and wide\u2010spread testing will help improve penetrance assessment of variants in these risk genes.<\/jats:p>","DOI":"10.1002\/ijc.30428","type":"journal-article","created":{"date-parts":[[2016,9,12]],"date-time":"2016-09-12T09:09:04Z","timestamp":1473671344000},"page":"95-102","source":"Crossref","is-referenced-by-count":104,"title":["Gene panel sequencing in familial breast\/ovarian cancer patients identifies multiple novel mutations also in genes others than BRCA1\/2"],"prefix":"10.1002","volume":"140","author":[{"given":"Cornelia","family":"Kraus","sequence":"first","affiliation":[{"name":"Institute of Human Genetics, University Hospital Erlangen, Friedrich\u2010Alexander\u2010Universit\u00e4t Erlangen\u2010N\u00fcrnberg (FAU) Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliane","family":"Hoyer","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University Hospital Erlangen, Friedrich\u2010Alexander\u2010Universit\u00e4t Erlangen\u2010N\u00fcrnberg (FAU) Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgia","family":"Vasileiou","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University Hospital Erlangen, Friedrich\u2010Alexander\u2010Universit\u00e4t Erlangen\u2010N\u00fcrnberg (FAU) Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marius","family":"Wunderle","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics University Hospital Erlangen, Comprehensive Cancer Center Erlangen\u2010EMN, Friedrich\u2010Alexander\u2010Universit\u00e4t Erlangen\u2010N\u00fcrnberg (FAU) Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Lux","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics University Hospital Erlangen, Comprehensive Cancer Center Erlangen\u2010EMN, Friedrich\u2010Alexander\u2010Universit\u00e4t Erlangen\u2010N\u00fcrnberg (FAU) Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4885-8471","authenticated-orcid":false,"given":"Peter A.","family":"Fasching","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics University Hospital Erlangen, Comprehensive Cancer Center Erlangen\u2010EMN, Friedrich\u2010Alexander\u2010Universit\u00e4t Erlangen\u2010N\u00fcrnberg (FAU) Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mandy","family":"Krumbiegel","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University Hospital Erlangen, Friedrich\u2010Alexander\u2010Universit\u00e4t Erlangen\u2010N\u00fcrnberg (FAU) Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Uebe","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University Hospital Erlangen, Friedrich\u2010Alexander\u2010Universit\u00e4t Erlangen\u2010N\u00fcrnberg (FAU) Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Reuter","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University Hospital Erlangen, Friedrich\u2010Alexander\u2010Universit\u00e4t Erlangen\u2010N\u00fcrnberg (FAU) Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias W.","family":"Beckmann","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics University Hospital Erlangen, Comprehensive Cancer Center Erlangen\u2010EMN, Friedrich\u2010Alexander\u2010Universit\u00e4t Erlangen\u2010N\u00fcrnberg (FAU) Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Reis","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University Hospital Erlangen, Friedrich\u2010Alexander\u2010Universit\u00e4t Erlangen\u2010N\u00fcrnberg (FAU) Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,9,23]]},"reference":[{"key":"e_1_2_7_2_1","unstructured":"Cancer in Germany 2009\/2010. 9th edition. 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