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Genomic and transcriptomic changes complement each other in the pathogenesis of sporadic Burkitt lymphoma

Author

Listed:
  • Cristina López

    (Ulm University and Ulm University Medical Center
    Christian-Albrechts-University)

  • Kortine Kleinheinz

    (German Cancer Research Center (DKFZ)
    University of Heidelberg)

  • Sietse M. Aukema

    (Christian-Albrechts-University
    Christian-Albrechts-University)

  • Marius Rohde

    (University Hospital Giessen)

  • Stephan H. Bernhart

    (University of Leipzig
    University of Leipzig
    University of Leipzig)

  • Daniel Hübschmann

    (German Cancer Research Center (DKFZ)
    University Hospital
    Heidelberg, Germany and Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH))

  • Rabea Wagener

    (Ulm University and Ulm University Medical Center
    Christian-Albrechts-University)

  • Umut H. Toprak

    (German Cancer Research Center (DKFZ)
    German Cancer Research Center (DKFZ)
    Heidelberg University)

  • Francesco Raimondi

    (University of Heidelberg)

  • Markus Kreuz

    (Institute for Medical Informatics Statistics and Epidemiology)

  • Sebastian M. Waszak

    (EMBL Heidelberg)

  • Zhiqin Huang

    (German Cancer Research Center (DKFZ))

  • Lina Sieverling

    (Heidelberg University
    German Cancer Research Center (DKFZ))

  • Nagarajan Paramasivam

    (German Cancer Research Center (DKFZ)
    Heidelberg University)

  • Julian Seufert

    (German Cancer Research Center (DKFZ))

  • Stephanie Sungalee

    (EMBL Heidelberg)

  • Robert B. Russell

    (University of Heidelberg)

  • Julia Bausinger

    (Ulm University and Ulm University Medical Center)

  • Helene Kretzmer

    (University of Leipzig
    University of Leipzig
    University of Leipzig
    Max Planck Institute for Molecular Genetics)

  • Ole Ammerpohl

    (Ulm University and Ulm University Medical Center)

  • Anke K. Bergmann

    (Christian-Albrechts-University
    University Hospital Schleswig-Holstein)

  • Hans Binder

    (University of Leipzig
    University of Leipzig)

  • Arndt Borkhardt

    (Heinrich-Heine-University)

  • Benedikt Brors

    (German Cancer Research Center (DKFZ))

  • Alexander Claviez

    (University Hospital Schleswig-Holstein)

  • Gero Doose

    (University of Leipzig
    University of Leipzig
    University of Leipzig)

  • Lars Feuerbach

    (German Cancer Research Center (DKFZ))

  • Andrea Haake

    (Christian-Albrechts-University)

  • Martin-Leo Hansmann

    (University of Frankfurt Medical School)

  • Jessica Hoell

    (Heinrich-Heine-University)

  • Michael Hummel

    (Charité – University Medicine Berlin)

  • Jan O. Korbel

    (EMBL Heidelberg)

  • Chris Lawerenz

    (German Cancer Research Center (DKFZ))

  • Dido Lenze

    (Charité – University Medicine Berlin)

  • Bernhard Radlwimmer

    (German Cancer Research Center (DKFZ))

  • Julia Richter

    (Christian-Albrechts-University
    Christian-Albrechts-University)

  • Philip Rosenstiel

    (Christian-Albrechts-University)

  • Andreas Rosenwald

    (University of Würzburg)

  • Markus B. Schilhabel

    (Christian-Albrechts-University)

  • Harald Stein

    (Pathodiagnostik Berlin)

  • Stephan Stilgenbauer

    (Ulm University)

  • Peter F. Stadler

    (University of Leipzig)

  • Monika Szczepanowski

    (Christian-Albrechts-University)

  • Marc A. Weniger

    (University of Duisburg-Essen)

  • Marc Zapatka

    (German Cancer Research Center (DKFZ))

  • Roland Eils

    (German Cancer Research Center (DKFZ)
    University of Heidelberg)

  • Peter Lichter

    (German Cancer Research Center (DKFZ))

  • Markus Loeffler

    (Institute for Medical Informatics Statistics and Epidemiology)

  • Peter Möller

    (University of Ulm and University Hospital of Ulm)

  • Lorenz Trümper

    (Georg-August-University of Göttingen)

  • Wolfram Klapper

    (Christian-Albrechts-University)

  • Steve Hoffmann

    (University of Leipzig
    University of Leipzig
    University of Leipzig
    Leibniz Institute on Ageing-Fritz Lipmann Institut (FLI))

  • Ralf Küppers

    (University of Duisburg-Essen)

  • Birgit Burkhardt

    (University Hospital Münster - Pediatric Hematology and Oncology)

  • Matthias Schlesner

    (German Cancer Research Center (DKFZ)
    German Cancer Research Center (DKFZ))

  • Reiner Siebert

    (Ulm University and Ulm University Medical Center
    Christian-Albrechts-University)

Abstract

Burkitt lymphoma (BL) is the most common B-cell lymphoma in children. Within the International Cancer Genome Consortium (ICGC), we performed whole genome and transcriptome sequencing of 39 sporadic BL. Here, we unravel interaction of structural, mutational, and transcriptional changes, which contribute to MYC oncogene dysregulation together with the pathognomonic IG-MYC translocation. Moreover, by mapping IGH translocation breakpoints, we provide evidence that the precursor of at least a subset of BL is a B-cell poised to express IGHA. We describe the landscape of mutations, structural variants, and mutational processes, and identified a series of driver genes in the pathogenesis of BL, which can be targeted by various mechanisms, including IG-non MYC translocations, germline and somatic mutations, fusion transcripts, and alternative splicing.

Suggested Citation

  • Cristina López & Kortine Kleinheinz & Sietse M. Aukema & Marius Rohde & Stephan H. Bernhart & Daniel Hübschmann & Rabea Wagener & Umut H. Toprak & Francesco Raimondi & Markus Kreuz & Sebastian M. Wasz, 2019. "Genomic and transcriptomic changes complement each other in the pathogenesis of sporadic Burkitt lymphoma," Nature Communications, Nature, vol. 10(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08578-3
    DOI: 10.1038/s41467-019-08578-3
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    Cited by:

    1. 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.
    2. Weiyin Zhou & Anja Fischer & Martin D. Ogwang & Wen Luo & Patrick Kerchan & Steven J. Reynolds & Constance N. Tenge & Pamela A. Were & Robert T. Kuremu & Walter N. Wekesa & Nestory Masalu & Esther Kaw, 2023. "Mosaic chromosomal alterations in peripheral blood leukocytes of children in sub-Saharan Africa," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    3. Anja Fischer & Thomas K. Albert & Natalia Moreno & Marta Interlandi & Jana Mormann & Selina Glaser & Paurnima Patil & Flavia W. Faria & Mathis Richter & Archana Verma & Sebastian T. Balbach & Rabea Wa, 2024. "Lack of SMARCB1 expression characterizes a subset of human and murine peripheral T-cell lymphomas," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    4. Birgit Burkhardt & Ulf Michgehl & Jonas Rohde & Tabea Erdmann & Philipp Berning & Katrin Reutter & Marius Rohde & Arndt Borkhardt & Thomas Burmeister & Sandeep Dave & Alexandar Tzankov & Martin Dugas , 2022. "Clinical relevance of molecular characteristics in Burkitt lymphoma differs according to age," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

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