Pedrosa, LucíaFernández-Miranda, IsmaelPérez-Callejo, DavidQuero, CristinaRodríguez, MartaMartín-Acosta, PalomaGómez, SagrarioGonzález-Rincón, JuliaSantos, AdriánTarin, CarlosGarcía, Juan FGarcía-Arroyo, Francisco RRueda, AntonioCamacho, Francisca IGarcía-Cosío, MónicaHeredero, AnaLlanos, MartaMollejo, ManuelaPiris-Villaespesa, MiguelGómez-Codina, JoséYanguas-Casás, NataliaSánchez, AntonioPiris, Miguel AProvencio, MarianoSánchez-Beato, Margarita2023-02-092023-02-092021-01-21http://hdl.handle.net/10668/17020Diffuse 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.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/AdultAgedAlgorithmsAntineoplastic Combined Chemotherapy ProtocolsCD79 AntigensDNA-Binding ProteinsFemaleHumansIn Situ Hybridization, FluorescenceLymphoma, Large B-Cell, DiffuseMaleMiddle AgedMutationNeoplasm ProteinsOutcome Assessment, Health CarePrognosisReceptor, Notch1Reproducibility of ResultsRituximabresearch article33479306open access10.1038/s41598-020-80376-02045-2322PMC7820010https://www.nature.com/articles/s41598-020-80376-0.pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820010/pdf