{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:44:20Z","timestamp":1760060660519,"version":"build-2065373602"},"reference-count":16,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T00:00:00Z","timestamp":1757289600000},"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>Background: Copy number variations (CNVs), also referred to as large genomic rearrangements (LGRs), represent a crucial component of BRCA1\/2 (BRCA) testing. Next-generation sequencing (NGS) has become an established approach for detecting LGRs by combining sequencing data with dedicated bioinformatics pipelines. However, CNV detection in formalin-fixed paraffin-embedded (FFPE) samples remains technically challenging, and there is the need to implement a robust and optimized analysis strategy for routine clinical practice. Methods: This study evaluated 40 FFPE ovarian cancer (OC) samples from patients undergoing BRCA testing. The performance of the amplicon-based NGS Diatech Myriapod\u00ae NGS BRCA1\/2 panel (Diatech Pharmacogenetics, Jesi, Italy) was assessed for its ability to detect BRCA CNVs and results were compared to two hybrid capture-based reference assays. Results: Among the 40 analyzed samples (17 CNV-positive and 23 CNV-negative for BRCA genes), the Diatech pipeline showed a good concordance with the reference method\u2014all CNVs were correctly identified in 16 cases with good enough sequencing quality. Only one result was inconclusive due to low sequencing quality. Conclusions: These findings support the clinical utility of NGS-based CNV analysis in FFPE samples when combined with appropriate bioinformatics tools. Integrating visual inspection of CNV plots with automated CNV calling improves the reliability of CNV detection and enhances the interpretation of results from tumor tissue. Accurate CNV detection directly from tumor tissue may reduce the need for additional germline testing, thus shortening turnaround times. Nevertheless, blood-based testing remains mandatory to determine whether detected BRCA CNVs are of hereditary or somatic origin, particularly in cases with a strong clinical suspicion of inherited predisposition due to young age and a personal and\/or family history of OC.<\/jats:p>","DOI":"10.3390\/genes16091052","type":"journal-article","created":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T08:40:15Z","timestamp":1757407215000},"page":"1052","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Detection of Clinically Significant BRCA Large Genomic Rearrangements in FFPE Ovarian Cancer Samples: A Comparative NGS Study"],"prefix":"10.3390","volume":"16","author":[{"given":"Alessia","family":"Perrucci","sequence":"first","affiliation":[{"name":"Departmental Unit of Molecular and Genomic Diagnostics, Fondazione Policlinico Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Genomics Core Facility, G-STeP, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"De Bonis","sequence":"additional","affiliation":[{"name":"Departmental Unit of Molecular and Genomic Diagnostics, Fondazione Policlinico Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Genomics Core Facility, G-STeP, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6455-8973","authenticated-orcid":false,"given":"Giulia","family":"Maneri","sequence":"additional","affiliation":[{"name":"Departmental Unit of Molecular and Genomic Diagnostics, Fondazione Policlinico Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Genomics Core Facility, G-STeP, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio","family":"Ricciardi Tenore","sequence":"additional","affiliation":[{"name":"Departmental Unit of Molecular and Genomic Diagnostics, Fondazione Policlinico Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Genomics Core Facility, G-STeP, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0523-5744","authenticated-orcid":false,"given":"Paola","family":"Concolino","sequence":"additional","affiliation":[{"name":"Departmental Unit of Molecular and Genomic Diagnostics, Fondazione Policlinico Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Genomics Core Facility, G-STeP, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matteo","family":"Corsi","sequence":"additional","affiliation":[{"name":"Departmental Unit of Molecular and Genomic Diagnostics, Fondazione Policlinico Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Genomics Core Facility, G-STeP, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Conca","sequence":"additional","affiliation":[{"name":"Departmental Unit of Molecular and Genomic Diagnostics, Fondazione Policlinico Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Genomics Core Facility, G-STeP, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Evangelista","sequence":"additional","affiliation":[{"name":"Departmental Unit of Molecular and Genomic Diagnostics, Fondazione Policlinico Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Genomics Core Facility, G-STeP, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7164-4952","authenticated-orcid":false,"given":"Alessia","family":"Piermattei","sequence":"additional","affiliation":[{"name":"Pathology Unit, Department of Woman and Child\u2019s Health and Public Health Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4442-4046","authenticated-orcid":false,"given":"Camilla","family":"Nero","sequence":"additional","affiliation":[{"name":"Unit of Oncological Gynecology, Department of Women, Children and Public Health Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Department of Women, Children and Public Health Sciences Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0657-4323","authenticated-orcid":false,"given":"Luciano","family":"Giac\u00f2","sequence":"additional","affiliation":[{"name":"Bioinformatics Research Core Facility, Gemelli Science and Technology Park (G-STeP), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0780-0153","authenticated-orcid":false,"given":"Elisa","family":"De Paolis","sequence":"additional","affiliation":[{"name":"Departmental Unit of Molecular and Genomic Diagnostics, Fondazione Policlinico Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Genomics Core Facility, G-STeP, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5579-335X","authenticated-orcid":false,"given":"Anna","family":"Fagotti","sequence":"additional","affiliation":[{"name":"Unit of Oncological Gynecology, Department of Women, Children and Public Health Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Department of Women, Children and Public Health Sciences Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0833-4334","authenticated-orcid":false,"given":"Angelo","family":"Minucci","sequence":"additional","affiliation":[{"name":"Departmental Unit of Molecular and Genomic Diagnostics, Fondazione Policlinico Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Genomics Core Facility, G-STeP, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, 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