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It has been widely used in genetic diagnosis of several inherited diseases, and, in clinical oncology, it may enhance the discovery of new susceptibility genes and enable individualized care of cancer patients. In this context, we explored a pan-cancer panel in the investigation of germline variants in Brazilian patients presenting clinical criteria for hereditary cancer syndromes or familial history.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Seventy-one individuals diagnosed or with familial history of hereditary cancer syndromes were submitted to custom pan-cancer panel including 16 high and moderate penetrance genes previously associated with hereditary cancer syndromes (<jats:italic>APC, BRCA1, BRCA2, CDH1, CDKN2A, CHEK2, MSH2, MSH6, MUTYH, PTEN, RB1, RET, TP53, VHL, XPA<\/jats:italic> and <jats:italic>XPC<\/jats:italic>). All pathogenic variants were validated by Sanger sequencing.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We identified a total of eight pathogenic variants among 12 of 71 individuals (16.9%). Among the mutation-positive subjects, 50% were diagnosed with breast cancer and had mutations in <jats:italic>BRCA1<\/jats:italic>, <jats:italic>CDH1<\/jats:italic> and <jats:italic>MUTYH<\/jats:italic>. Notably, 33.3% were individuals diagnosed with polyposis or who had family cases and harbored pathogenic mutations in <jats:italic>APC<\/jats:italic> and <jats:italic>MUTYH<\/jats:italic>. The remaining individuals (16.7%) were gastric cancer patients with pathogenic variants in <jats:italic>CDH1<\/jats:italic> and <jats:italic>MSH2<\/jats:italic>. Overall, 54 (76.05%) individuals presented at least one variant uncertain significance (VUS), totalizing 81 VUS. Of these, seven were predicted to have disease-causing potential.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Overall, analysis of all these genes in NGS-panel allowed the identification not only of pathogenic variants related to hereditary cancer syndromes but also of some VUS that need further clinical and molecular investigations. The results obtained in this study had a significant impact on patients and their relatives since it allowed genetic counselling and personalized management decisions.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12885-021-08089-9","type":"journal-article","created":{"date-parts":[[2021,4,7]],"date-time":"2021-04-07T12:03:19Z","timestamp":1617796999000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Comprehensive analysis of germline mutations in northern Brazil: a panel of 16 genes for hereditary cancer-predisposing syndrome investigation"],"prefix":"10.1186","volume":"21","author":[{"given":"Amanda Ferreira","family":"Vidal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafaella Sousa","family":"Ferraz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonette","family":"El-Husny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caio Santos","family":"Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Vinasco-Sandoval","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leandro","family":"Magalh\u00e3es","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milene","family":"Raiol-Moraes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Williams Fernandes","family":"Barra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia Lara Brito Lins","family":"Pereira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo Pimentel","family":"de Assump\u00e7\u00e3o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo Miranda","family":"de Brito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo Assun\u00e7\u00e3o","family":"Vialle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sidney","family":"Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c2ndrea","family":"Ribeiro-dos-Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 M.","family":"Ribeiro-dos-Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,4,7]]},"reference":[{"key":"8089_CR1","doi-asserted-by":"publisher","first-page":"e143","DOI":"10.1097\/AOG.0000000000003562","volume":"134","author":"Hereditary Cancer Syndromes and Risk Assessment","year":"2019","unstructured":"Hereditary Cancer Syndromes and Risk Assessment. 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