Gene Expression Profiling Provides an Improved Characterization of -Mutated Diffuse Large B-Cell Lymphomas.

: Diffuse large B-cell lymphomas (DLBCLs) are heterogeneous neoplasms. and mutations are associated with the activated B-cell-like (ABC) subtype of DLBCL and often co-occur and lead to constitutive activation of the NF-κB pathway. Several different genetic classifications to date have recognized - and -mutated DLBCLs as a unique subtype with poor response to therapy and unfavorable survival. However, little is known about gene expression in DLBCLs with mutated (and ) in comparison to their wild type counterparts. The objective of this study was to compare the gene expression in DLBCLs according to their mutational status. : A total of 48 primary, treatment-naïve DLBCLs (-mutated: 35%/n = 17, -wild type: 65%/n = 31) were investigated using RNA expression profiling (770 genes), followed by immunohistochemical analysis of the up-regulated genes and survival analysis. : The gene expression analysis revealed that downstream of CD79B and the NF-κB targets , , , and were up-regulated in -mutated DLBCLs. The strongest up-regulation was detected for and . Other up-regulated genes included the apoptosis-related and , as well as genes of cell cycle regulation such as , and . Up-regulation was also found for , , , and the subunit. mutation showed an association with poorer overall survival in a secondary analysis, consistent with prior reports, while survival by / mutation status and the differentially expressed genes showed no significant differences in this cohort. : In conclusion, the current study identified novel up-regulated genes in -mutated DLBCLs beyond NF-κB pathway signaling, which may contribute to a better definition of potential therapeutic targets and further improves the characterization of this distinct and aggressive DLBCL subgroup.