%0 Journal Article
%A Pedrosa, Lucía
%A Fernández-Miranda, Ismael
%A Pérez-Callejo, David
%A Quero, Cristina
%A Rodríguez, Marta
%A Martín-Acosta, Paloma
%A Gómez, Sagrario
%A González-Rincón, Julia
%A Santos, Adrián
%A Tarin, Carlos
%A García, Juan F
%A García-Arroyo, Francisco R
%A Rueda, Antonio
%A Camacho, Francisca I
%A García-Cosío, Mónica
%A Heredero, Ana
%A Llanos, Marta
%A Mollejo, Manuela
%A Piris-Villaespesa, Miguel
%A Gómez-Codina, José
%A Yanguas-Casás, Natalia
%A Sánchez, Antonio
%A Piris, Miguel A
%A Provencio, Mariano
%A Sánchez-Beato, Margarita
%T Proposal and validation of a method to classify genetic subtypes of diffuse large B cell lymphoma.
%D 2021
%U http://hdl.handle.net/10668/17020
%X 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 N12-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.
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