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DNA methylome analysis in Burkitt and follicular lymphomas identifies differentially methylated regions linked to somatic mutation and transcriptional control

2015; Nature Portfolio; Volume: 47; Issue: 11 Linguagem: Inglês

10.1038/ng.3413

1546-1718

Helene Kretzmer, Stephan Wolf, Wei Wang, Andrea Haake, Marc A. Weniger, Anke K. Bergmann, Matthew J. Betts, Enrique Carrillo de Santa Pau, Gero Doose, Jana Gutwein, Julia Richter, Volker Hovestadt, Bingding Huang, Daniel Rico, Frank Jühling, Julia Kolarova, Qianhao Lu, Christian Otto, Rabea Wagener, Judith Arnolds, Birgit Burkhardt, Alexander Claviez, Hans G. Drexler, Sonja Eberth, Roland Eils, Paul Flicek, Siegfried Haas, Michael Humme, Dennis Karsch, Hinrik H D Kerstens, Wolfram Klapper, Markus Kreuz, Chris Lawerenz, Dido Lenzek, Markus Loeffler, Cristina López, Roderick A.F. MacLeod, Joost H.A. Martens, Marta Kulis, José I. Martín‐Subero, Peter Möller, Inga Nage, Simone Picelli, Inga Vater, Marius Rohde, Philip Rosenstiel, Maciej Rosolowski, Robert B. Russell, Markus B. Schilhabel, Matthias Schlesner, Peter F. Stadler, Monika Szczepanowski, Lorenz Trümper, Hendrik G. Stunnenberg, Ralf Küppers, Ole Ammerpohl, Peter Lichter, Reiner Siebert, Steve Hoffmann, Bernhard Radlwimmer,

Viral-associated cancers and disorders

Although Burkitt lymphomas and follicular lymphomas both have features of germinal center B cells, they are biologically and clinically quite distinct. Here we performed whole-genome bisulfite, genome and transcriptome sequencing in 13 IG-MYC translocation-positive Burkitt lymphoma, nine BCL2 translocation-positive follicular lymphoma and four normal germinal center B cell samples. Comparison of Burkitt and follicular lymphoma samples showed differential methylation of intragenic regions that strongly correlated with expression of associated genes, for example, genes active in germinal center dark-zone and light-zone B cells. Integrative pathway analyses of regions differentially methylated in Burkitt and follicular lymphomas implicated DNA methylation as cooperating with somatic mutation of sphingosine phosphate signaling, as well as the TCF3-ID3 and SWI/SNF complexes, in a large fraction of Burkitt lymphomas. Taken together, our results demonstrate a tight connection between somatic mutation, DNA methylation and transcriptional control in key B cell pathways deregulated differentially in Burkitt lymphoma and other germinal center B cell lymphomas.