Recurrent mutation of the ID3 gene in Burkitt lymphoma identified by integrated genome, exome and transcriptome sequencing.

Authors:
Julia Richter, Matthias Schlesner, Steve Hoffmann, Markus Kreuz, Ellen Leich, Birgit Burkhardt, Maciej Rosolowski, Ole Ammerpohl, Rabea Wagener, Stephan H Bernhart, Dido Lenze, Monika Szczepanowski, Maren Paulsen, Simone Lipinski, Robert B Russell, Sabine Adam-Klages, Gordana Apic, Alexander Claviez, Dirk Hasenclever, Volker Hovestadt, Nadine Hornig, Jan O Korbel, Dieter Kube, David Langenberger, Chris Lawerenz, Jasmin Lisfeld, Katharina Meyer, Simone Picelli, Jordan Pischimarov, Bernhard Radlwimmer, Tobias Rausch, Marius Rohde, Markus Schilhabel, René Scholtysik, Rainer Spang, Heiko Trautmann, Thorsten Zenz, Arndt Borkhardt, Hans G Drexler, Peter Möller, Roderick A F MacLeod, Christiane Pott, Stefan Schreiber, Lorenz Trümper, Markus Loeffler, Peter F Stadler, Peter Lichter, Roland Eils, Ralf Küppers, Michael Hummel, Wolfram Klapper, Philip Rosenstiel, Andreas Rosenwald, Benedikt Brors, Reiner Siebert, - -
Year of publication:
2012
Volume:
44
Issue:
12
Issn:
1061-4036
Journal title abbreviated:
NAT GENET
Journal title long:
Nature genetics
Impact factor:
31.616
Abstract: 
Burkitt lymphoma is a mature aggressive B-cell lymphoma derived from germinal center B cells. Its cytogenetic hallmark is the Burkitt translocation t(8;14)(q24;q32) and its variants, which juxtapose the MYC oncogene with one of the three immunoglobulin loci. Consequently, MYC is deregulated, resulting in massive perturbation of gene expression. Nevertheless, MYC deregulation alone seems not to be sufficient to drive Burkitt lymphomagenesis. By whole-genome, whole-exome and transcriptome sequencing of four prototypical Burkitt lymphomas with immunoglobulin gene (IG)-MYC translocation, we identified seven recurrently mutated genes. One of these genes, ID3, mapped to a region of focal homozygous loss in Burkitt lymphoma. In an extended cohort, 36 of 53 molecularly defined Burkitt lymphomas (68%) carried potentially damaging mutations of ID3. These were strongly enriched at somatic hypermutation motifs. Only 6 of 47 other B-cell lymphomas with the IG-MYC translocation (13%) carried ID3 mutations. These findings suggest that cooperation between ID3 inactivation and IG-MYC translocation is a hallmark of Burkitt lymphomagenesis.