Comprehensive characterization of driver genes in diffuse large B cell lymphoma

Diffuse large B cell lymphoma (DLBCL) is the most common hematological malignancy and is one of the most frequent non-Hodgkin lymphomas. Large-scale genomic studies have defined genetic drivers of DLBCL and their association with functional and clinical outcomes. However, the lymphomagenesis of DLBCL is yet to be fully understood. In the present study, four computational tools OncodriveFM, OncodriveCLUST, integrated Cancer Genome Score and Driver Genes and Pathways were used to detect driver genes and driver pathways involved in DLBCL. The aforementioned tools were also used to perform an integrative investigation of driver genes, including co-expression network, protein-protein interaction, copy number variation and survival analyses. The present study identified 208 driver genes and 31 driver pathways in DLBCL.IGLL5, MLL2, BTG2, B2M, PIM1, CARD11were the top five frequently mutated genes in DLBCL.NOTCH3, LAMC1, COL4A1, PDGFRBandKDRwere the 5 hub genes in the blue module that were associated with patient age.TP53, MYC, EGFR, PTEN, IL6, STAT3, MAPK8, TNFandCDH1were at the core of the protein-protein interaction network.PRDM1, CDKN2A, CDKN2B, TNFAIP3, RSPO3were the top five frequently deleted driver genes in DLBCL, whileACTB, BTG2, PLET1, CARD11, DIXDC1were the top five frequently amplified driver genes in DLBCL. HighEIF3B, MLH1, PPP1CAandRECQL4expression was associated with decreased overall survival rate of patients with DLBCL. HighXPO1andLYNexpression were associated with increased overall survival rate of patients with DLBCL. The present study improves the understanding of the biological processes and pathways involved in lymphomagenesis. The driver genes,EIF3B, MLH1, PPP1CA, RECQL4, XPO1andLYN, pave the way for developing prognostic biomarkers and new therapeutic strategies for DLBCL.