Genetic and transcriptomic analyses of diffuse large B‐cell lymphoma patients with poor outcomes within two years of diagnosis

Background: R-CHOP immunochemotherapy is the first-line treatment for DLBCL, but approximately 30%–40% of patients still experience refractory or relapsed (R/R) disease. We aimed to characterize molecular features DLBCL derived from with early R/R disease and develop a prognosis model identify those high-risk patients. Methods: performed comprehensive genomic transcriptomic characterization on 161 R-CHOP-treated samples. These were grouped by follow-up outcome status after treatment. The first group had within two years diagnosis (poor outcome; n = 50), second remained in remission at following (good 111). In an addition, external cohorts included validation analysis (GSE117556, 374; GSE181063, 810). Results: Patients poor outcomes more often advanced stage disease, high international prognostic index (IPI) non-GCB subtype tumor. identified set frequent somatically mutated targets (Figure 1A), including PIM1, TP53, MPEG1 ROBO1, as well specific mutational signature (activation-induced cytidine deaminase related) DLBCLs outcomes. Transcriptomic analyses further showed distinct gene expression pattern less inflamed tumor microenvironment these 1B). Finally, we developed 11-gene independent marker treated 1C). could stratify based their IPI scores 1D). Additionally, use was also validated cohorts, suggesting robustness risk model. Furthermore, our effectively patients, double-hit MCD genetic subtypes that are associated survival FIGURE 1 (A) mutation between good DLBCLs. (B) Tumor-infiltrating immune cells (C-D) Kaplan–Meier PFS low-risk groups (C) association (D). Keywords: Aggressive B-cell non-Hodgkin lymphoma, Diagnostic Prognostic Biomarkers, Genomics, Epigenomics, Other -Omics No conflicts interests pertinent abstract.