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)

<b>Background</b>: 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. <b>Methods</b>: 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 <i>TP53</i> mutation. Time to first relapse or progression of disease (POD) was used as the primary outcome measure. <b>Results</b>: We identified CNVs associated with MCL, with Del 9p21.3 (<i>CDKN2A</i>) being the strongest predictor of shorter time to POD (<i>p</i> = 0.01), independently of <i>TP53</i> mutation in multivariable analysis. Unsupervised clustering identified molecularly defined clusters that were associated with significantly different times to POD (<i>p</i> = 0.01). Pairwise log-rank tests confirmed <i>TP53</i> mutated vs. wild-type (WT) as the strongest prognostic factor, with cluster assessment improving the prognostic predictivity among patients: clusters <i>TP53</i>-mut vs. <i>TP53</i>-WT, <i>p</i> = 0.001, HR = 3.92; and <i>p</i> = 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 <i>TP53</i> mutation.

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Journal
Cancers
Published
2025-12-17
DOI
https://doi.org/10.3390/cancers17244027
Primary Topic
Lymphoma Diagnosis and Treatment
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article
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article

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)

Simona Gambino, Marilisa Galasso, Luca Nassi, Maurilio Ponzoni et al.
Cancers
Lymphoma Diagnosis and Treatment
article

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)

Simona Gambino, Marilisa Galasso, Luca Nassi, Maurilio Ponzoni, Elisa Lucchini, Alessia Castellino, Barbara Famengo, Riccardo Moia, Pietro Bulian, Maria Chiara Tisi, Vittorio Ruggero Zilioli, Alberto Fabbri, Alessandro Re, Carlo Visco, Alessia Moioli, Luisa Lorenzi, Maria Teresa Scupoli, Francesco Piazza, Jacopo Olivieri, Simone Ragaini, Antonino Aparo, Francesca Maria Quaglia, Piero Maria Stefani, Annalisa Arcari, Maria Elena Carazzolo, Angela Ferrari, Alice Parisi, Vittoria Salaorni
article en

Abstract

<b>Background</b>: 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. <b>Methods</b>: 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 <i>TP53</i> mutation. Time to first relapse or progression of disease (POD) was used as the primary outcome measure. <b>Results</b>: We identified CNVs associated with MCL, with Del 9p21.3 (<i>CDKN2A</i>) being the strongest predictor of shorter time to POD (<i>p</i> = 0.01), independently of <i>TP53</i> mutation in multivariable analysis. Unsupervised clustering identified molecularly defined clusters that were associated with significantly different times to POD (<i>p</i> = 0.01). Pairwise log-rank tests confirmed <i>TP53</i> mutated vs. wild-type (WT) as the strongest prognostic factor, with cluster assessment improving the prognostic predictivity among patients: clusters <i>TP53</i>-mut vs. <i>TP53</i>-WT, <i>p</i> = 0.001, HR = 3.92; and <i>p</i> = 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 <i>TP53</i> mutation.

CancersVol. 17(24)
University of Verona (IT), Università degli Studi del Piemonte Orientale “Amedeo Avogadro” (IT), University of Udine (IT), University of Padua (IT), Vita-Salute San Raffaele University (IT), Azienda Sanitaria Unità Locale di Reggio Emilia (IT), Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda (IT), AULSS 2 Marca Trevigiana (IT), Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (IT), Presidio Ospedaliero (IT), Centro di Riferimento Oncologico (IT), Azienda Ospedaliera Universitaria Senese (IT), Azienda Sanitaria Ospedaliera S.Croce e Carle Cuneo (IT), Guglielmo da Saliceto Hospital (IT), Azienda Ospedale - Università Padova (IT), Ospedale San Bortolo (IT), Azienda Sanitaria Universitaria Integrata di Trieste (IT), University of Florence (IT), University of Turin (IT), University of Brescia (IT)
Openalex Percentile: Top 44%
Lymphoma Diagnosis and Treatment
DOIOpen Access PDFOpenAlex
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