1. Proposal and validation of a method to classify genetic subtypes of diffuse large B cell lymphoma.
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Pedrosa, Lucía, Fernández-Miranda, Ismael, Pérez-Callejo, David, Quero, Cristina, Rodríguez, Marta, Martín-Acosta, Paloma, Gómez, Sagrario, González-Rincón, Julia, Santos, Adrián, Tarin, Carlos, García, Juan F., García-Arroyo, Francisco R., Rueda, Antonio, Camacho, Francisca I., García-Cosío, Mónica, Heredero, Ana, Llanos, Marta, Mollejo, Manuela, Piris-Villaespesa, Miguel, and Gómez-Codina, José
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LYMPHOMAS ,RITUXIMAB ,GENETIC mutation ,DISEASE relapse ,FOLLOW-up studies (Medicine) - Abstract
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease whose prognosis is associated with clinical features, cell-of-origin and genetic aberrations. Recent integrative, multi-omic analyses had led to identifying overlapping genetic DLBCL subtypes. We used targeted massive sequencing to analyze 84 diagnostic samples from a multicenter cohort of patients with DLBCL treated with rituximab-containing therapies and a median follow-up of 6 years. The most frequently mutated genes were IGLL5 (43%), KMT2D (33.3%), CREBBP (28.6%), PIM1 (26.2%), and CARD11 (22.6%). Mutations in CD79B were associated with a higher risk of relapse after treatment, whereas patients with mutations in CD79B, ETS1, and CD58 had a significantly shorter survival. Based on the new genetic DLBCL classifications, we tested and validated a simplified method to classify samples in five genetic subtypes analyzing the mutational status of 26 genes and BCL2 and BCL6 translocations. We propose a two-step genetic DLBCL classifier (2-S), integrating the most significant features from previous algorithms, to classify the samples as N1
2-S , EZB2-S , MCD2-S , BN22-S , and ST22-S groups. We determined its sensitivity and specificity, compared with the other established algorithms, and evaluated its clinical impact. The results showed that ST22-S is the group with the best clinical outcome and N12-S , the more aggressive one. EZB2-S identified a subgroup with a worse prognosis among GCB-DLBLC cases. [ABSTRACT FROM AUTHOR]- Published
- 2021
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