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

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 i
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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Author:Cristina López, Kortine Kleinheinz, Sietse M. Aukema, Marius Rohde, Stephan H. Bernhart, Daniel Hübschmann, Rabea Wagener, Umut H. Toprak, Francesco Raimondi, Markus Kreuz, Sebastian Martin 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 Höll, Michael Hummel, Jan Oliver 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 Andrèe Weniger, Marc Zapatka, Roland Eils, Peter Lichter, Markus Löffler, Peter Möller, Lorenz Trümper, Wolfram Klapper, Steve Hoffmann, Ralf Küppers, Birgit Burkhardt, Matthias Schlesner, Reiner Siebert
URN:urn:nbn:de:hebis:30:3-502633
DOI:http://dx.doi.org/10.1038/s41467-019-08578-3
ISSN:2041-1723
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=30926794
Parent Title (English):Nature Communications
Publisher:Nature Publishing Group UK
Place of publication:[London]
Document Type:Article
Language:English
Year of Completion:2019
Date of first Publication:2019/03/29
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Contributing Corporation:ICGC MMML-Seq Consortium
Release Date:2019/05/20
Tag:Cancer genomics; Lymphocytes; Lymphoid tissues; Oncology
Volume:10
Issue:1, Art. 1459
Pagenumber:19
First Page:1
Last Page:19
Note:
Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
HeBIS PPN:450966356
Institutes:Medizin
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0

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