This study presents an analysis of the coding genome of diffuse large B-cell lymphoma (DLBCL), revealing a high mutation burden and complex genetic alterations. Using next-generation sequencing and copy number analysis, researchers identified an average of more than 30 clonally represented gene alterations per case. Mutations were found in genes not previously linked to DLBCL, including those involved in chromatin methylation and immune recognition by T cells. The study also identified recurrent mutations in genes such as MLL2, which is involved in histone methylation, and in genes related to immune recognition, such as B2M. These findings suggest that dysregulated pathways involving chromatin modification and immune recognition play a central role in DLBCL pathogenesis. Additionally, copy number alterations were detected in various genes, indicating a heterogeneous genetic landscape in DLBCL. The study highlights the importance of understanding the genetic complexity of DLBCL to develop targeted therapies. Overall, the results provide new insights into the genetic basis of DLBCL and may contribute to the identification of novel therapeutic targets.This study presents an analysis of the coding genome of diffuse large B-cell lymphoma (DLBCL), revealing a high mutation burden and complex genetic alterations. Using next-generation sequencing and copy number analysis, researchers identified an average of more than 30 clonally represented gene alterations per case. Mutations were found in genes not previously linked to DLBCL, including those involved in chromatin methylation and immune recognition by T cells. The study also identified recurrent mutations in genes such as MLL2, which is involved in histone methylation, and in genes related to immune recognition, such as B2M. These findings suggest that dysregulated pathways involving chromatin modification and immune recognition play a central role in DLBCL pathogenesis. Additionally, copy number alterations were detected in various genes, indicating a heterogeneous genetic landscape in DLBCL. The study highlights the importance of understanding the genetic complexity of DLBCL to develop targeted therapies. Overall, the results provide new insights into the genetic basis of DLBCL and may contribute to the identification of novel therapeutic targets.