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The genomic and transcriptional landscape of primary central nervous system lymphoma

Author

Listed:
  • Josefine Radke

    (Humboldt-Universität zu Berlin, Berlin Institute of Health
    German Cancer Consortium (DKTK), Partner Site Charité Berlin
    Universitätsmedizin Greifswald)

  • Naveed Ishaque

    (Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin)

  • Randi Koll

    (Humboldt-Universität zu Berlin, Berlin Institute of Health
    German Cancer Consortium (DKTK), Partner Site Charité Berlin)

  • Zuguang Gu

    (Molecular Precision Oncology Program, NCT Heidelberg)

  • Elisa Schumann

    (Humboldt-Universität zu Berlin, Berlin Institute of Health
    German Cancer Consortium (DKTK), Partner Site Charité Berlin)

  • Lina Sieverling

    (German Cancer Research Center (DKFZ)
    National Center for Tumor Diseases (NCT))

  • Sebastian Uhrig

    (Molecular Precision Oncology Program, NCT Heidelberg
    Molecular Diagnostics Program, NCT Heidelberg)

  • Daniel Hübschmann

    (Molecular Precision Oncology Program, NCT Heidelberg
    Molecular Diagnostics Program, NCT Heidelberg
    Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH)
    University Hospital)

  • Umut H. Toprak

    (Division Neuroblastoma Genomics, German Cancer Research Center (DKFZ))

  • Cristina López

    (Ulm University & Ulm University Medical Center
    Institut d’Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), CIBER de Cáncer)

  • Xavier Pastor Hostench

    (Molecular Precision Oncology Program, NCT Heidelberg)

  • Simone Borgoni

    (German Cancer Research Center (DKFZ))

  • Dilafruz Juraeva

    (Molecular Precision Oncology Program, NCT Heidelberg)

  • Fabienne Pritsch

    (Humboldt-Universität zu Berlin, Berlin Institute of Health
    German Cancer Consortium (DKTK), Partner Site Charité Berlin)

  • Nagarajan Paramasivam

    (Molecular Precision Oncology Program, NCT Heidelberg)

  • Gnana Prakash Balasubramanian

    (Hopp Children’s Cancer Center, NCT Heidelberg (KiTZ)
    Division of Pediatric Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ))

  • Matthias Schlesner

    (German Cancer Research Center (DKFZ)
    Augsburg University)

  • Shashwat Sahay

    (Universitätsmedizin Greifswald
    Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin)

  • Marc Weniger

    (Institute of Cell Biology (Cancer Research), Medical Faculty, University of Duisburg-Essen
    German Cancer Consortium (DKTK), Partner Site Essen)

  • Debora Pehl

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

  • Helena Radbruch

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

  • Anja Osterloh

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

  • Agnieszka Korfel

    (Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health)

  • Martin Misch

    (Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health)

  • Julia Onken

    (Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health)

  • Katharina Faust

    (Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health)

  • Peter Vajkoczy

    (Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health)

  • Dag Moskopp

    (Vivantes Klinikum im Friedrichshain)

  • Yawen Wang

    (Vivantes Klinikum im Friedrichshain)

  • Andreas Jödicke

    (Vivantes Klinikum Neukölln)

  • Lorenz Trümper

    (Georg-Augusts-University of Göttingen)

  • Ioannis Anagnostopoulos

    (Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health)

  • Dido Lenze

    (Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health)

  • Ralf Küppers

    (Institute of Cell Biology (Cancer Research), Medical Faculty, University of Duisburg-Essen
    German Cancer Consortium (DKTK), Partner Site Essen)

  • Michael Hummel

    (Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health)

  • Clemens A. Schmitt

    (Johannes Kepler University, Kepler Universitätsklinikum
    Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health)

  • Otmar D. Wiestler

    (German Cancer Research Center (DKFZ))

  • Stephan Wolf

    (German Cancer Research Center (DKFZ))

  • Andreas Unterberg

    (University Hospital Heidelberg)

  • Roland Eils

    (Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin)

  • Christel Herold-Mende

    (University Hospital Heidelberg)

  • Benedikt Brors

    (Molecular Precision Oncology Program, NCT Heidelberg)

  • Reiner Siebert

    (Ulm University & Ulm University Medical Center)

  • Stefan Wiemann

    (German Cancer Consortium (DKTK)
    German Cancer Research Center (DKFZ))

  • Frank L. Heppner

    (Humboldt-Universität zu Berlin, Berlin Institute of Health
    German Cancer Consortium (DKTK), Partner Site Charité Berlin
    Cluster of Excellence, NeuroCure
    German Center for Neurodegenerative Diseases (DZNE) Berlin)

Abstract

Primary lymphomas of the central nervous system (PCNSL) are mainly diffuse large B-cell lymphomas (DLBCLs) confined to the central nervous system (CNS). Molecular drivers of PCNSL have not been fully elucidated. Here, we profile and compare the whole-genome and transcriptome landscape of 51 CNS lymphomas (CNSL) to 39 follicular lymphoma and 36 DLBCL cases outside the CNS. We find recurrent mutations in JAK-STAT, NFkB, and B-cell receptor signaling pathways, including hallmark mutations in MYD88 L265P (67%) and CD79B (63%), and CDKN2A deletions (83%). PCNSLs exhibit significantly more focal deletions of HLA-D (6p21) locus as a potential mechanism of immune evasion. Mutational signatures correlating with DNA replication and mitosis are significantly enriched in PCNSL. TERT gene expression is significantly higher in PCNSL compared to activated B-cell (ABC)-DLBCL. Transcriptome analysis clearly distinguishes PCNSL and systemic DLBCL into distinct molecular subtypes. Epstein-Barr virus (EBV)+ CNSL cases lack recurrent mutational hotspots apart from IG and HLA-DRB loci. We show that PCNSL can be clearly distinguished from DLBCL, having distinct expression profiles, IG expression and translocation patterns, as well as specific combinations of genetic alterations.

Suggested Citation

  • Josefine Radke & Naveed Ishaque & Randi Koll & Zuguang Gu & Elisa Schumann & Lina Sieverling & Sebastian Uhrig & Daniel Hübschmann & Umut H. Toprak & Cristina López & Xavier Pastor Hostench & Simone B, 2022. "The genomic and transcriptional landscape of primary central nervous system lymphoma," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30050-y
    DOI: 10.1038/s41467-022-30050-y
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