{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T02:47:45Z","timestamp":1774579665433,"version":"3.50.1"},"reference-count":49,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T00:00:00Z","timestamp":1750377600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hereditary breast and ovarian cancer (HBOC) syndrome is primarily associated with mutations in BRCA1 and BRCA2, but increasing evidence links it to other malignancies, including male breast, prostate, and pancreatic cancers. Advances in genetic testing have led to the use of multigene panels, revealing that additional genes contribute to HBOC risk. We tested 280 patients with suspected HBOC using a multigene panel including BRCA1, BRCA2, and other genes involved in homologous recombination (HR) and additional DNA repair mechanisms. Variants were classified as pathogenic variants (PVs), variants of uncertain significance (VUS), or novel. In silico tools were used to predict the clinical relevance of VUS and novel variants. The clinical phenotype of families carrying a PV was evaluated. PVs were identified in 19.3% of patients: 8.9% in BRCA1\/2 and 10.4% in other genes, mainly CHEK2, ATM, PALB2, and BRIP1. An additional 1.8% of cases harbored likely pathogenic VUS or novel variants according to bioinformatic prediction. Breast and ovarian cancer were the most frequent malignancies in our population, both in the BRCA group and in those with PVs in other susceptibility genes. Broad genetic testing beyond BRCA improves HBOC diagnostics, supports identification of at-risk families, and enables more personalized surveillance and treatment.<\/jats:p>","DOI":"10.3390\/ijms26135928","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T06:10:27Z","timestamp":1750399827000},"page":"5928","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Expanding the Genomic Landscape of HBOC and Cancer Risk Among Mutation Carriers"],"prefix":"10.3390","volume":"26","author":[{"given":"Maria Teresa","family":"Vietri","sequence":"first","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, S. Andrea delle Dame, Via L. De Crecchio, 7, 80138 Napoli, Italy"},{"name":"Unit of Clinical and Molecular Pathology, AOU University of Campania \u201cLuigi Vanvitelli\u201d, S. Andrea delle Dame, Via L. De Crecchio, 7, 80138 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8664-6210","authenticated-orcid":false,"given":"Chiara","family":"Della Pepa","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, S. Andrea delle Dame, Via L. De Crecchio, 7, 80138 Napoli, Italy"},{"name":"Oncology Unit, Vallo Della Lucania-Agropoli Hospital, ASL Salerno, Via F Cammarota, 84078 Vallo Della Lucania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gemma","family":"Caliendo","sequence":"additional","affiliation":[{"name":"Unit of Clinical and Molecular Pathology, AOU University of Campania \u201cLuigi Vanvitelli\u201d, S. Andrea delle Dame, Via L. De Crecchio, 7, 80138 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessia","family":"Mignano","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, S. Andrea delle Dame, Via L. De Crecchio, 7, 80138 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luisa","family":"Albanese","sequence":"additional","affiliation":[{"name":"Unit of Clinical and Molecular Pathology, AOU University of Campania \u201cLuigi Vanvitelli\u201d, S. Andrea delle Dame, Via L. De Crecchio, 7, 80138 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marialaura","family":"Zitiello","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, S. Andrea delle Dame, Via L. De Crecchio, 7, 80138 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marianna","family":"Stilo","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, S. Andrea delle Dame, Via L. De Crecchio, 7, 80138 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna Maria","family":"Molinari","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, S. Andrea delle Dame, Via L. De Crecchio, 7, 80138 Napoli, Italy"},{"name":"Unit of Clinical and Molecular Pathology, AOU University of Campania \u201cLuigi Vanvitelli\u201d, S. Andrea delle Dame, Via L. De Crecchio, 7, 80138 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Lee, Y.C., Lee, Y.L., and Li, C.Y. (2021). BRCA Genes and Related Cancers: A Meta-Analysis from Epidemiological Cohort Studies. Medicina, 57.","DOI":"10.3390\/medicina57090905"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Vietri, M.T., Caliendo, G., D\u2019Elia, G., Resse, M., Casamassimi, A., Minucci, P.B., Dello Ioio, C., Cioffi, M., and Molinari, A.M. (2020). Five Italian Families with Two Mutations in BRCA Genes. Genes, 11.","DOI":"10.3390\/genes11121451"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.eururo.2019.08.025","article-title":"Prostate Cancer Risks for Male BRCA1 and BRCA2 Mutation Carriers: A Prospective Cohort Study","volume":"77","author":"Nyberg","year":"2020","journal-title":"Eur. 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