RT Journal Article
T1 Proposal and validation of a method to classify genetic subtypes of diffuse large B cell lymphoma.
A1 Pedrosa, Lucía
A1 Fernández-Miranda, Ismael
A1 Pérez-Callejo, David
A1 Quero, Cristina
A1 Rodríguez, Marta
A1 Martín-Acosta, Paloma
A1 Gómez, Sagrario
A1 González-Rincón, Julia
A1 Santos, Adrián
A1 Tarin, Carlos
A1 García, Juan F
A1 García-Arroyo, Francisco R
A1 Rueda, Antonio
A1 Camacho, Francisca I
A1 García-Cosío, Mónica
A1 Heredero, Ana
A1 Llanos, Marta
A1 Mollejo, Manuela
A1 Piris-Villaespesa, Miguel
A1 Gómez-Codina, José
A1 Yanguas-Casás, Natalia
A1 Sánchez, Antonio
A1 Piris, Miguel A
A1 Provencio, Mariano
A1 Sánchez-Beato, Margarita
AB 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.
YR 2021
FD 2021-01-21
LK http://hdl.handle.net/10668/17020
UL http://hdl.handle.net/10668/17020
LA en
DS RISalud
RD Apr 7, 2025