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Molecular and functional profiling identifies therapeutically targetable vulnerabilities in plasmablastic lymphoma

Author

Listed:
  • Fabian Frontzek

    (University Hospital Münster)

  • Annette M. Staiger

    (Stuttgart and University of Tuebingen
    Robert Bosch Hospital)

  • Myroslav Zapukhlyak

    (University Hospital Münster)

  • Wendan Xu

    (University Hospital Münster)

  • Irina Bonzheim

    (University Hospital Tübingen)

  • Vanessa Borgmann

    (University Hospital Tübingen)

  • Philip Sander

    (University Hospital Tübingen)

  • Maria Joao Baptista

    (Universitat Autònoma de Barcelona)

  • Jan-Niklas Heming

    (University Hospital Münster)

  • Philipp Berning

    (University Hospital Münster)

  • Ramona Wullenkord

    (University Hospital Münster)

  • Tabea Erdmann

    (University Hospital Münster)

  • Mathias Lutz

    (University Hospital Münster)

  • Pia Veratti

    (University Hospital Freiburg)

  • Sophia Ehrenfeld

    (University of Freiburg)

  • Kirsty Wienand

    (University Medical Center Göttingen)

  • Heike Horn

    (Stuttgart and University of Tuebingen
    Robert Bosch Hospital)

  • John R. Goodlad

    (Queen Elizabeth University Hospital)

  • Matthew R. Wilson

    (Beatson West of Scotland Cancer Centre)

  • Ioannis Anagnostopoulos

    (University of Würzburg
    Humboldt-Universität zu Berlin and Berlin Institute of Health)

  • Mario Lamping

    (Humboldt-Universität zu Berlin and Berlin Institute of Health)

  • Eva Gonzalez-Barca

    (L’Hospitalet de Llobregat)

  • Fina Climent

    (L’Hospitalet de Llobregat)

  • Antonio Salar

    (Hospital del Mar)

  • Josep Castellvi

    (Hospital Universitari Vall d’Hebron)

  • Pau Abrisqueta

    (Hospital Universitari Vall d’Hebron)

  • Javier Menarguez

    (Hospital Gregorio Marañón)

  • Teresa Aldamiz

    (Hospital Gregorio Marañón)

  • Julia Richter

    (Christian-Albrechts-University)

  • Wolfram Klapper

    (Christian-Albrechts-University)

  • Alexandar Tzankov

    (University Hospital Basel)

  • Stefan Dirnhofer

    (University Hospital Basel)

  • Andreas Rosenwald

    (University of Würzburg)

  • José Luis Mate

    (Universitat Autònoma de Barcelona)

  • Gustavo Tapia

    (Universitat Autònoma de Barcelona)

  • Peter Lenz

    (University of Marburg)

  • Cornelius Miething

    (University of Freiburg
    Partner Site Freiburg
    German Cancer Research Center (DKFZ))

  • Wolfgang Hartmann

    (University Hospital Münster)

  • Björn Chapuy

    (University Medical Center Göttingen)

  • Falko Fend

    (University Hospital Tübingen)

  • German Ott

    (Robert Bosch Hospital)

  • José-Tomas Navarro

    (Universitat Autònoma de Barcelona)

  • Michael Grau

    (University Hospital Münster)

  • Georg Lenz

    (University Hospital Münster)

Abstract

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.

Suggested Citation

  • Fabian Frontzek & Annette M. Staiger & Myroslav Zapukhlyak & Wendan Xu & Irina Bonzheim & Vanessa Borgmann & Philip Sander & Maria Joao Baptista & Jan-Niklas Heming & Philipp Berning & Ramona Wullenko, 2021. "Molecular and functional profiling identifies therapeutically targetable vulnerabilities in plasmablastic lymphoma," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25405-w
    DOI: 10.1038/s41467-021-25405-w
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