Gene Expression Profiling Provides an Improved Characterization of CD79B-Mutated Diffuse Large B-Cell Lymphomas

<b>Background and Objectives</b>: Diffuse large B-cell lymphomas (DLBCLs) are heterogeneous neoplasms. <i>CD79B</i> and <i>MYD88</i> 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 <i>CD79B</i>- and <i>MYD88</i>-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 <i>CD79B</i> (and <i>MYD88</i>) in comparison to their wild type counterparts. The objective of this study was to compare the gene expression in DLBCLs according to their <i>CD79B</i> mutational status. <b>Methods</b>: A total of 48 primary, treatment-naïve DLBCLs (<i>CD79B</i>-mutated: 35%/n = 17, <i>CD79B</i>-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. <b>Results</b>: The gene expression analysis revealed that downstream of CD79B <i>CARD11</i> and the NF-κB targets <i>NFKBIZ</i>, <i>IL10</i>, <i>IL12A</i>, <i>PIM1</i> and <i>BCL2A1</i> were up-regulated in <i>CD79B</i>-mutated DLBCLs. The strongest up-regulation was detected for <i>ARNT2</i> and <i>WNT11</i>. Other up-regulated genes included the apoptosis-related <i>BID</i> and <i>granzyme B</i>, as well as genes of cell cycle regulation such as <i>RUNX1</i>, <i>RUNX1T1</i> and <i>RASGRF1</i>. Up-regulation was also found for <i>IL7</i>, <i>STAT3</i>, <i>MLLT4</i>, <i>CD14</i> and the <i>HSP90B1</i> subunit. <i>TP53</i> mutation showed an association with poorer overall survival in a secondary analysis, consistent with prior reports, while survival by <i>CD79B</i>/<i>MYD88</i> mutation status and the differentially expressed genes showed no significant differences in this cohort. <b>Conclusions</b>: In conclusion, the current study identified novel up-regulated genes in <i>CD79B</i>-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.