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

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. Waszak, Zhiqin Huang, Lina Sieverling, Nagarajan Paramasivam, Julian Seufert, Stephanie Sungalee, Robert B. Russell, Julia Bausinger, Helene Kretzmer, Ole Ammerpohl, Anke K. Bergmann, Hans Binder, Arndt Borkhardt, Benedikt Brors, Alexander Claviez, Gero Doose, Lars Feuerbach, Andrea Haake, Martin-Leo Hansmann, Jessica Hoell, Michael Hummel, Jan O. Korbel, Chris Lawerenz, Dido Lenze, Bernhard Radlwimmer, Julia Richter, Philip Rosenstiel, Andreas Rosenwald, Markus B. Schilhabel, Harald Stein, Stephan Stilgenbauer, Peter F. Stadler, Monika Szczepanowski, Marc A. Weniger, Marc Zapatka, Roland Eils, Peter Lichter, Markus Loeffler, Peter Möller, Lorenz Trümper, Wolfram Klapper, Steve Hoffmann, Ralf Küppers, Birgit Burkhardt, Matthias Schlesner () and Reiner Siebert ()
Additional contact information
Cristina López: Ulm University and Ulm University Medical Center
Kortine Kleinheinz: German Cancer Research Center (DKFZ)
Sietse M. Aukema: Christian-Albrechts-University
Marius Rohde: University Hospital Giessen
Stephan H. Bernhart: University of Leipzig
Daniel Hübschmann: German Cancer Research Center (DKFZ)
Rabea Wagener: Ulm University and Ulm University Medical Center
Umut H. Toprak: German Cancer Research Center (DKFZ)
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
Nagarajan Paramasivam: German Cancer Research Center (DKFZ)
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
Ole Ammerpohl: Ulm University and Ulm University Medical Center
Anke K. Bergmann: Christian-Albrechts-University
Hans Binder: 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
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
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)
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
Ralf Küppers: University of Duisburg-Essen
Birgit Burkhardt: University Hospital Münster - Pediatric Hematology and Oncology
Matthias Schlesner: German Cancer Research Center (DKFZ)
Reiner Siebert: Ulm University and Ulm University Medical Center

Nature Communications, 2019, vol. 10, issue 1, 1-19

Abstract: 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.

Date: 2019
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08578-3

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DOI: 10.1038/s41467-019-08578-3

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