EBV-Positive and EBV-Negative Posttransplant Diffuse Large B Cell Lymphomas Have Distinct Genomic and Transcriptomic Features

The molecular pathogenesis of posttransplant diffuse large B cell lymphoma (PT-DLBCL) is largely unknown. We have recently shown that Epstein-Barr virus-positive (EBV+) and -negative (EBV-) PT-DLBCL have distinct gene expression profiles, and the transcriptomic profile of EBV- PT-DLBCL is similar to that of DLBCL in immunocompetent individuals (IC-DLBCL). To validate these observations at the genomic level, we performed array-comparative genome hybridization (aCGH) analysis of 21 EBV+ PT-DLBCL, 6 EBV- PT-DLBCL, and 11 control IC-DLBCL, and subsequently combined genomic and transcriptomic data. The analysis showed that EBV+ and EBV- PT-DLBCL have distinct aCGH profiles and shared only one recurrent imbalance. EBV- PT-DLBCL, however, displayed at least 10 aberrations recurrent in IC-DLBCL, among which characteristic gain of 3/3q and 18q, and loss of 6q23/TNFAIP3 as well as 9p21/CDKN2A. The most prevalent aberration in EBV+ PT-DLBCL was gain/amplification of 9p24.1 targeting PDCD1LG2/PDL2. Our data indicate that the FOXP1 oncogene and the tumor suppressor CDKNA2 implicated in EBV- DLBCL, do not play a critical role in the pathogenesis of EBV+ PT-DLBCL. Altogether, genomic profiling of PT-/IC-DLBCL confirms that EBV- and EBV+ PT-DLBCL are distinct entities, while EBV- PT-DLBCL has features in common with IC-DLBCL. These findings support the hypothesis that EBV- PT-DLBCL are de novo lymphomas in transplant recipients.