1. Proposal and validation of a method to classify genetic subtypes of diffuse large B cell lymphoma.
- Author
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Pedrosa L, Fernández-Miranda I, Pérez-Callejo D, Quero C, Rodríguez M, Martín-Acosta P, Gómez S, González-Rincón J, Santos A, Tarin C, García JF, García-Arroyo FR, Rueda A, Camacho FI, García-Cosío M, Heredero A, Llanos M, Mollejo M, Piris-Villaespesa M, Gómez-Codina J, Yanguas-Casás N, Sánchez A, Piris MA, Provencio M, and Sánchez-Beato M
- Subjects
- Adult, Aged, CD79 Antigens genetics, DNA-Binding Proteins genetics, Female, Humans, In Situ Hybridization, Fluorescence, Lymphoma, Large B-Cell, Diffuse classification, Male, Middle Aged, Neoplasm Proteins genetics, Outcome Assessment, Health Care methods, Outcome Assessment, Health Care statistics & numerical data, Prognosis, Receptor, Notch1 genetics, Reproducibility of Results, Rituximab administration & dosage, Algorithms, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Lymphoma, Large B-Cell, Diffuse drug therapy, Lymphoma, Large B-Cell, Diffuse genetics, Mutation
- 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.- Published
- 2021
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