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, Reiner Siebert

• 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. WeBurkitt 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.…