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

Richter, Julia, Schlesner, Matthias, Hoffmann, Steve, Kreuz, Markus, Leich, Ellen, Burkhardt, Birgit, Rosolowski, Maciej, Ammerpohl, Ole, Wagener, Rabea, Bernhart, Stephan H., Lenze, Dido, Szczepanowski, Monika, Paulsen, Maren, Lipinski, Simone, Russell, Robert B., Adam-Klages, Sabine, Apic, Gordana, Claviez, Alexander, Hasenclever, Dirk, Hovestadt, Volker, Hornig, Nadine, Korbel, Jan O., Kube, Dieter, Langenberger, David, Lawerenz, Chris, Lisfeld, Jasmin, Meyer, Katharina, Picelli, Simone, Pischimarov, Jordan, Radlwimmer, Bernhard, Rausch, Tobias, Rohde, Marius, Schilhabel, Markus, Scholtysik, Rene, Spang, Rainer, Trautmann, Heiko, Zenz, Thorsten, Borkhardt, Arndt, Drexler, Hans G., Moeller, Peter, MacLeod, Roderick A. F., Pott, Christiane, Schreiber, Stefan, Truemper, Lorenz, Loeffler, Markus, Stadler, Peter F., Lichter, Peter, Eils, Roland, Kueppers, Ralf, Hummel, Michael, Klapper, Wolfram, Rosenstiel, Philip, Rosenwald, Andreas, Brors, Benedikt and Siebert, Reiner (2012) Recurrent mutation of the ID3 gene in Burkitt lymphoma identified by integrated genome, exome and transcriptome sequencing Nature Genetics, 44 (12). pp. 1316-1320.

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Abstract

Burkitt lymphoma is a mature aggressive B-cell lymphoma derived from germinal center B cells(1). 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(2). Consequently, MYC is deregulated, resulting in massive perturbation of gene expression(3). 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(4). 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.

Document Type: Article
Research affiliation: Kiel University
OceanRep > The Future Ocean - Cluster of Excellence
Kiel University > Kiel Marine Science
Refereed: Yes
ISSN: 1061-4036
Projects: Future Ocean
Date Deposited: 14 May 2014 09:39
Last Modified: 14 May 2014 09:39
URI: http://eprints.uni-kiel.de/id/eprint/24225

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