{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:30:39Z","timestamp":1790627439574,"version":"4.1.0"},"reference-count":92,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,7,21]],"date-time":"2022-07-21T00:00:00Z","timestamp":1658361600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Germline pathogenic variants (PVs) in oncogenes and tumour suppressor genes are responsible for 5 to 10% of all diagnosed cancers, which are commonly known as hereditary cancer predisposition syndromes (HCPS). A total of 104 individuals at high risk of HCPS were selected by genetic counselling for genetic testing in the past 2 years. Most of them were subjects having a personal and family history of breast cancer (BC) selected according to current established criteria. Genes analysis involved in HCPS was assessed by next-generation sequencing (NGS) using a custom cancer panel with high- and moderate-risk susceptibility genes. Germline PVs were identified in 17 of 104 individuals (16.3%) analysed, while variants of uncertain significance (VUS) were identified in 21\/104 (20.2%) cases. Concerning the germline PVs distribution among the 13 BC individuals with positive findings, 8\/13 (61.5%) were in the BRCA1\/2 genes, whereas 5\/13 (38.4%) were in other high- or moderate-risk genes including PALB2, TP53, ATM and CHEK2. NGS genetic testing showed that 6\/13 (46.1%) of the PVs observed in BC patients were detected in triple-negative BC. Interestingly, the likelihood of carrying the PVs in the moderate-to-high-risk genes calculated by the cancer risk model BOADICEA was significantly higher in pathogenic variant carriers than in negative subjects. Collectively, this study shows that multigene panel testing can offer an effective diagnostic approach for patients at high risk of hereditary cancers.<\/jats:p>","DOI":"10.3390\/genes13071286","type":"journal-article","created":{"date-parts":[[2022,7,21]],"date-time":"2022-07-21T10:36:56Z","timestamp":1658399816000},"page":"1286","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Germline Testing in a Cohort of Patients at High Risk of Hereditary Cancer Predisposition Syndromes: First Two-Year Results from South Italy"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0916-8101","authenticated-orcid":false,"given":"Francesco","family":"Paduano","sequence":"first","affiliation":[{"name":"Medical Genetics Unit, Mater Domini University Hospital, 88100 Catanzaro, Italy"},{"name":"Department of Health Sciences, Campus S. Venuta, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy"},{"name":"Stem Cells and Medical Genetics Units, Tecnologica Research Institute and Marrelli Health, 88900 Crotone, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5451-593X","authenticated-orcid":false,"given":"Emma","family":"Colao","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Mater Domini University Hospital, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda","family":"Fabiani","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Mater Domini University Hospital, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Rocca","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Mater Domini University Hospital, 88100 Catanzaro, Italy"},{"name":"Department of Experimental and Clinical Medicine, Campus S. Venuta, University Magna Graecia of Catanzaro, Viale Europa, Localit\u00e0 Germaneto, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Dinatolo","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Mater Domini University Hospital, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adele","family":"Dattola","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Mater Domini University Hospital, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"D\u2019Antona","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Mater Domini University Hospital, 88100 Catanzaro, Italy"},{"name":"Department of Health Sciences, Campus S. Venuta, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosario","family":"Amato","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Mater Domini University Hospital, 88100 Catanzaro, Italy"},{"name":"Department of Health Sciences, Campus S. Venuta, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Trapasso","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Mater Domini University Hospital, 88100 Catanzaro, Italy"},{"name":"Department of Experimental and Clinical Medicine, Campus S. Venuta, University Magna Graecia of Catanzaro, Viale Europa, Localit\u00e0 Germaneto, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8976-8088","authenticated-orcid":false,"given":"Francesco","family":"Baudi","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Mater Domini University Hospital, 88100 Catanzaro, Italy"},{"name":"Department of Health Sciences, Campus S. Venuta, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Perrotti","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Mater Domini University Hospital, 88100 Catanzaro, Italy"},{"name":"Department of Health Sciences, Campus S. Venuta, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8524-7402","authenticated-orcid":false,"given":"Rodolfo","family":"Iuliano","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Mater Domini University Hospital, 88100 Catanzaro, Italy"},{"name":"Department of Health Sciences, Campus S. Venuta, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Tsaousis, G.N., Papadopoulou, E., Apessos, A., Agiannitopoulos, K., Pepe, G., Kampouri, S., Diamantopoulos, N., Floros, T., Iosifidou, R., and Katopodi, O. (2019). Analysis of hereditary cancer syndromes by using a panel of genes: Novel and multiple pathogenic mutations. 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