2026-05-22T00:07:01Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/182382024-09-21T21:58:15Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927col_20.500.12105_16964
Repisalud
author
Pedrosa, Lucía
author
Fernández-Miranda, Ismael
author
Pérez-Callejo, David
author
Quero, Cristina
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Rodríguez, Marta
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Martín-Acosta, Paloma
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Gómez, Sagrario
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González-Rincón, Julia
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Santos, Adrián
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Tarin, Carlos
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García, Juan F
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García-Arroyo, Francisco R
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Rueda, Antonio
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Camacho, Francisca I
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García-Cosío, Mónica
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Heredero, Ana
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Llanos, Marta
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Mollejo, Manuela
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Piris-Villaespesa, Miguel
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Gómez-Codina, José
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Yanguas-Casás, Natalia
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Sánchez, Antonio
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Piris, Miguel A
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Provencio, Mariano
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Sánchez-Beato, Margarita
2024-02-19T15:24:49Z
2024-02-19T15:24:49Z
2021-01-21
10.1038/s41598-020-80376-0
2045-2322
Scientific reports
http://hdl.handle.net/10668/17020
33479306
http://hdl.handle.net/20.500.12105/18238
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.
eng
Proposal and validation of a method to classify genetic subtypes of diffuse large B cell lymphoma.
research article