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oai:recercat.cat:2445/1802562025-11-20T14:58:00Zcom_2072_1057col_2072_478916col_2072_478917

Molecular and functional profiling identifies therapeutically targetable vulnerabilities in plasmablastic lymphoma Frontzek, Fabian Staiger, Annette M. Zapukhlyak, Myroslav Xu, Wendan Bonzheim, Irina Borgmann, Vanessa Sander, Philip Baptista, Maria Joao Heming, Jan-Niklas Berning, Philipp Wullenkord, Ramona Erdmann, Tabea Lutz, Mathias Veratti, Pia Ehrenfeld, Sophia Wienand, Kirsty Horn, Heike Goodlad, John R. Wilson, Matthew R. Anagnostopoulos, Ioannis Lamping, Mario González Barca, Eva Climent, Fina Salar, Antonio Castellvi, Josep Abrisqueta Costa, Pau Menarguez, Javier Aldamiz, Teresa Richter, Julia Klapper, Wolfram Tzankov, Alexandar Dirnhofer, Stefan Rosenwald, Andreas Mate, José L. Tapia, Gustavo Lenz, Peter Miething, Cornelius Hartmann, Wolfgang Chapuy, Björn Fend, Falko Ott, German Navarro, José-Tomás Grau, Michael Lenz, Georg Cèl·lules B Càncer Mapatge cromosòmic humà B cells Cancer Human gene mapping 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. 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. 2021-09-27T13:06:54Z 2021-09-27T13:06:54Z 2021-08-31 2021-09-23T09:04:51Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 2041-1723 https://hdl.handle.net/2445/180256 34465776 eng Reproducció del document publicat a: https://doi.org/10.1038/s41467-021-25405-w Nature Communications, 2021, vol. 12, num. 1 https://doi.org/10.1038/s41467-021-25405-w cc by (c) Frontzek, Fabian et al, 2021 http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess 14 p. application/pdf application/pdf Springer Science and Business Media LLC Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))