Genomic and transcriptomic changes complement each other in the pathogenesis of sporadic Burkitt lymphoma
Cristina López(Universität Ulm), Kortine Kleinheinz(German Cancer Research Center), Sietse Aukema(Christian-Albrechts-Universität zu Kiel), Marius Rohde(Universitätsklinikum Gießen und Marburg), Stephan Wolf(Leipzig University), Daniel Hübschmann(German Cancer Research Center), Rabea Wagener(Universität Ulm), Umut H. Toprak(German Cancer Research Center), Francesco Raimondi(Heidelberg University), Markus Kreuz, Sebastian M. Waszak(European Molecular Biology Organization), Zhiqin Huang(German Cancer Research Center), Lina Sieverling(German Cancer Research Center), Nagarajan Paramasivam(German Cancer Research Center), Julian Seufert(German Cancer Research Center), Stéphanie Sungalee(European Molecular Biology Organization), Robert B. Russell(Heidelberg University), Julia Bausinger(Universität Ulm), Helene Kretzmer(Max Planck Institute for Molecular Genetics), Ole Ammerpohl(Universität Ulm), Anke K. Bergmann(Christian-Albrechts-Universität zu Kiel), Hans Binder(Leipzig University), Arndt Borkhardt(Heinrich Heine University Düsseldorf), Benedikt Brors(German Cancer Research Center), Alexander Claviez(University Hospital Schleswig-Holstein), Gero Doose(Leipzig University), Lars Feuerbach(German Cancer Research Center), Andrea Haake(Christian-Albrechts-Universität zu Kiel), Martin‐Leo Hansmann(Goethe University Frankfurt), Jessica I. Hoell(Heinrich Heine University Düsseldorf), Michael Hummel(Berlin Institute of Health at Charité - Universitätsmedizin Berlin), Jan O. Korbel(European Molecular Biology Organization), Chris Lawerenz(German Cancer Research Center), Dido Lenze(Berlin Institute of Health at Charité - Universitätsmedizin Berlin), Bernhard Radlwimmer(German Cancer Research Center), Julia Richter(Christian-Albrechts-Universität zu Kiel), Philip Rosenstiel(Christian-Albrechts-Universität zu Kiel), Andreas Rosenwald(University of Würzburg), Markus B. Schilhabel(Christian-Albrechts-Universität zu Kiel), Harald Stein(Pathodiagnostik Berlin), Stephan Stilgenbauer(Universität Ulm), Peter F. Stadler(Leipzig University), Monika Szczepanowski(Christian-Albrechts-Universität zu Kiel), Marc A. Weniger(University of Duisburg-Essen), Marc Zapatka(German Cancer Research Center), Roland Eils(German Cancer Research Center), Peter Lichter(German Cancer Research Center), Markus Loeffler, Peter Mӧller(Universität Ulm), Lorenz Trümper(University of Göttingen), Wolfgang Hiddemann(Christian-Albrechts-Universität zu Kiel), Susanne Wagner(Christian-Albrechts-Universität zu Kiel), Gesine Richter(Christian-Albrechts-Universität zu Kiel), Jürgen Eils(German Cancer Research Center), Jules N. A. Kerssemakers(German Cancer Research Center), Christina Jaeger-Schmidt(German Cancer Research Center), Ingrid Scholz(German Cancer Research Center), Christoph Borst(Friedrich-Ebert-Krankenhaus), Friederike Braulke(University of Göttingen), Martin Dreyling, Sonja Eberth, Hermann Einsele(University of Würzburg), Norbert Frickhofen(Helios Dr. Horst Schmidt Kliniken Wiesbaden), Siegfried Haas(Friedrich-Ebert-Krankenhaus), Dennis Karsch(Clinical Research Center Kiel), Nicole Klepl(University of Göttingen), Michael Kneba(Clinical Research Center Kiel), Jasmin Lisfeld(University Hospital Münster), Luisa Mantovani‐Löffler(Klinikum St. Georg), German Ott(Robert Bosch Hospital), Christina Stadler(University of Göttingen), Peter Staib(Sankt-Antonius-Hospital Eschweiler), Thorsten Zenz(National Center for Tumor Diseases), Dieter Kube(University of Göttingen), Ulrike Kostezka(University Hospital Ulm), Vera Binder(Heinrich Heine University Düsseldorf), Ellen Leich(University of Würzburg), Inga Nagel(Christian-Albrechts-Universität zu Kiel), Jordan Pischimariov(University of Würzburg), Stefan Schreiber(Christian-Albrechts-Universität zu Kiel), Inga Vater(Christian-Albrechts-Universität zu Kiel), Lydia Hopp(Leipzig University), David Langenberger(Leipzig University), Maciej Rosołowski, Steve Hoffmann(Leibniz Institute on Aging - Fritz Lipmann Institute (FLI)), Ralf Küppers(University of Duisburg-Essen), Birgit Burkhardt(University Hospital Münster), Matthias Schlesner(German Cancer Research Center), Reiner Siebert(Universität Ulm)
Cited by 153Open Access
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.
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