Molecular and functional profiling of plasmablastic lymphoma

Plasmablastic lymphoma (PBL) represents a rare and aggressive lymphoma subtype frequently associated with immunosuppression. Clinically, patients with PBL are characterized by poor outcome. The current understanding of the molecular pathogenesis is limited. A hallmark of PBL represents its plasmacytic differentiation with loss of B-cell markers and, in 60% of cases, its association with Epstein-Barr virus (EBV). Roughly 50% of PBLs harbor a MYC translocation. We provide the first comprehensive integrated analysis using whole exome sequencing and copy number determination in a large cohort of primary PBL samples. We identified previously unknown alterations and high-level amplifications and characterized the functional impact of these aberrations using an unbiased shRNA screen in a PBL model. These analyses identified specific pathways as promising molecular targets to improve outcome of PBL patients.EGA study EGAS00001004659