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)
Year: 2025
Type: article
Abstract: 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.
Source: Cancers
Authors: Maria Elena Carazzolo, Francesca Maria Quaglia, Antonino Aparo, Alessia Moioli, Alice Parisi, Riccardo Moia, Francesco Piazza, Alessandro Re, Maria Chiara Tisi, Luca Nassi, Pietro Bulian, Alessia Castellino, Vittorio Ruggero Zilioli, Piero Maria Stefani, Alberto Fabbri, Elisa Lucchini, Annalisa Arcari, Luisa Lorenzi, Barbara Famengo, Maurilio Ponzoni, Angela Ferrari, Simone Ragaini, Jacopo Olivieri, Vittoria Salaorni, Simona Gambino, Marilisa Galasso, Maria Teresa Scupoli, Carlo Visco
Institutions: University of Verona, Azienda Ospedaliera Universitaria Integrata Verona, Università degli Studi del Piemonte Orientale “Amedeo Avogadro”, Azienda Ospedaliero Universitaria Maggiore della Carita, University of Padua, Azienda Ospedale - Università Padova, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, Ospedale San Bortolo, Azienda Ospedaliero-Universitaria Careggi, University of Florence, Centro di Riferimento Oncologico, Azienda Sanitaria Ospedaliera S.Croce e Carle Cuneo, Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda, Azienda Ospedaliera Universitaria Senese, Azienda sanitaria universitaria Giuliano Isontina, Azienda Unità Sanitaria Locale Piacenza, Guglielmo da Saliceto Hospital, University of Brescia, Vita-Salute San Raffaele University, IRCCS Ospedale San Raffaele, Azienda Sanitaria Unità Locale di Reggio Emilia, University of Turin, Azienda sanitaria universitaria Friuli Centrale
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,499
OpenAlex ID: W4417453203