{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:34:03Z","timestamp":1790393643834,"version":"4.1.0"},"reference-count":44,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondazione Italiana Linfomi (FIL), Fondazione Giulia Maramotti, Fondazione GRADE and Leu-kemia and Lymphoma Society","award":["Premio Giovani Ricercatori, Edition 2019 to F.M.Q. (MANTLE-FIRST BIO study, https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04882475)"],"award-info":[{"award-number":["Premio Giovani Ricercatori, Edition 2019 to F.M.Q. (MANTLE-FIRST BIO study, https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04882475)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Mantle Cell Lymphoma (MCL) is an aggressive malignancy with variable clinical behavior, largely reflecting the underlying molecular heterogeneity. The genomic landscape of MCL encompasses gene mutations with strong prognostic implications and secondary genetic events, which are also implicated in the pathogenesis and prognosis of the disease. Methods: We evaluated the diagnostic samples of 73 patients with relapsed\/refractory MCL that were enrolled in the Fondazione Italiana Linfomi Mantle First-BIO study. All patients had available data for correlating CNVs with the presence of TP53 mutation. Time to first relapse or progression of disease (POD) was used as the primary outcome measure. Results: We identified CNVs associated with MCL, with Del 9p21.3 (CDKN2A) being the strongest predictor of shorter time to POD (p = 0.01), independently of TP53 mutation in multivariable analysis. Unsupervised clustering identified molecularly defined clusters that were associated with significantly different times to POD (p = 0.01). Pairwise log-rank tests confirmed TP53 mutated vs. wild-type (WT) as the strongest prognostic factor, with cluster assessment improving the prognostic predictivity among patients: clusters TP53-mut vs. TP53-WT, p = 0.001, HR = 3.92; and p = 0.014, HR = 2.23, respectively. In conclusion, CNV-based molecular clusters might represent a novel approach to identify patients at higher risk of treatment failure, further contributing to the prognostic predictivity of TP53 mutation.<\/jats:p>","DOI":"10.3390\/cancers17244027","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T09:15:21Z","timestamp":1766049321000},"page":"4027","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Secondary Genetic Events and Their Relationship to TP53 Mutation in Mantle Cell Lymphoma: A Sub-Study from the FIL_MANTLE-FIRST BIO on Behalf of Fondazione Italiana Linfomi (FIL)"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-2742-2779","authenticated-orcid":false,"given":"Maria Elena","family":"Carazzolo","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Verona, 37134 Verona, Italy"},{"name":"Research Center LURM (Interdepartmental Laboratory of Medical Research), University of Verona, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4347-3775","authenticated-orcid":false,"given":"Francesca Maria","family":"Quaglia","sequence":"additional","affiliation":[{"name":"UOC di Ematologia, DAI Medico Generale, AOUI Verona, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4107-6680","authenticated-orcid":false,"given":"Antonino","family":"Aparo","sequence":"additional","affiliation":[{"name":"Research Center LURM (Interdepartmental Laboratory of Medical Research), University of Verona, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8650-4941","authenticated-orcid":false,"given":"Alessia","family":"Moioli","sequence":"additional","affiliation":[{"name":"UOC di Ematologia, DAI Medico Generale, AOUI Verona, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Parisi","sequence":"additional","affiliation":[{"name":"Department of Pathology and Diagnostics, University Hospital of Verona, 37126 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Moia","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale and AOU Maggiore della Carit\u00e0 di Novara, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2831-623X","authenticated-orcid":false,"given":"Francesco","family":"Piazza","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Padova and Unit of Hematology, Azienda Ospedale Universit\u00e0 Padova, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1156-6395","authenticated-orcid":false,"given":"Alessandro","family":"Re","sequence":"additional","affiliation":[{"name":"UOC Ematologia, Spedali Civili di Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Chiara","family":"Tisi","sequence":"additional","affiliation":[{"name":"Hematology Unit, San Bortolo Hospital, 36100 Vicenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Nassi","sequence":"additional","affiliation":[{"name":"Department of Hematology, Careggi Hospital and University of Florence, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Bulian","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico di Aviano, Istituto di Ricovero e Cura a Carattere 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