Sistema de Salut de Catalunya
Institut Català de la Salut
[Frontzek F, Zapukhlyak M, Xu W] Department of Medicine A, Department of Hematology, Oncology and Pneumology, University Hospital Münster, Münster, Germany. [Staiger AM] Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart and University of Tuebingen, Tübingen, Germany. Department of Clinical Pathology, Robert Bosch Hospital, Stuttgart, Germany. [Bonzheim I, Borgmann V] Institute of Pathology and Neuropathology, Eberhard Karls University of TübingenComprehensive Cancer Center, University Hospital Tübingen, Tübingen, Germany. [Castellvi J] Servei de Patologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Abrisqueta P] Servei d’Hematologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
2022-04-25T10:18:34Z
2022-04-25T10:18:34Z
2021-08-31
B-cell lymphoma; Cancer genetics
Linfoma de células B; Genética del cáncer
Limfoma de cèl·lules B; Genètica del càncer
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.
Open Access funding enabled and organized by Projekt DEAL.
Article
Published version
English
Cèl·lules B - Tumors - Tractament; Seqüència de nucleòtids; Sistema limfàtic - Càncer - Mortalitat; DISEASES::Neoplasms::Neoplasms by Histologic Type::Lymphoma::Lymphoma, Non-Hodgkin::Lymphoma, B-Cell::Lymphoma, Large B-Cell, Diffuse::Plasmablastic Lymphoma; Other subheadings::Other subheadings::/therapy; ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Investigative Techniques::Genetic Techniques::Sequence Analysis::Sequence Analysis, DNA::Whole Genome Sequencing::Whole Exome Sequencing; ENFERMEDADES::neoplasias::neoplasias por tipo histológico::linfoma::linfoma no Hodgkin::linfoma de células B::linfoma de células B grandes difuso::linfoma plasmablástico; Otros calificadores::Otros calificadores::/terapia; TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::técnicas de investigación::técnicas genéticas::análisis de secuencias::análisis de secuencias de ADN::secuenciación del genoma completo::secuenciación del exoma completo
Nature Research
Nature Communications;12
https://doi.org/10.1038/s41467-021-25405-w
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
Articles científics - HVH [3440]
