Frontzek, FabianStaiger, Annette M.Zapukhlyak, MyroslavXu, WendanBonzheim, IrinaBorgmann, VanessaSander, PhilipBaptista, Maria JoaoHeming, Jan-NiklasBerning, PhilippWullenkord, RamonaErdmann, TabeaLutz, MathiasVeratti, PiaEhrenfeld, SophiaWienand, KirstyHorn, HeikeGoodlad, John R.Wilson, Matthew R.Anagnostopoulos, IoannisLamping, MarioGonzález Barca, EvaCliment, FinaSalar, AntonioCastellvi, JosepAbrisqueta Costa, PauMenarguez, JavierAldamiz, TeresaRichter, JuliaKlapper, WolframTzankov, AlexandarDirnhofer, StefanRosenwald, AndreasMate, José L.Tapia, GustavoLenz, PeterMiething, CorneliusHartmann, WolfgangChapuy, BjörnFend, FalkoOtt, GermanNavarro, José-TomásGrau, MichaelLenz, Georg2021-09-272021-09-272021-08-312041-1723https://hdl.handle.net/2445/180256Plasmablastic 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. Here, we provide a comprehensive integrated genomic analysis using whole exome sequencing (WES) and genome-wide copy number determination in a large cohort of 96 primary PBL samples. We identify alterations activating the RAS-RAF, JAK-STAT, and NOTCH pathways as well as frequent high-level amplifications in MCL1 and IRF4. The functional impact of these alterations is assessed using an unbiased shRNA screen in a PBL model. These analyses identify the IRF4 and JAK-STAT pathways as promising molecular targets to improve outcome of PBL patients.14 p.application/pdfengcc by (c) Frontzek, Fabian et al, 2021http://creativecommons.org/licenses/by/3.0/es/Cèl·lules BCàncerMapatge cromosòmic humàB cellsCancerHuman gene mappinginfo:eu-repo/semantics/article2021-09-23info:eu-repo/semantics/openAccess34465776