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Nat Genet. 2015 Nov;47(11):1316-1325. doi: 10.1038/ng.3413. Epub 2015 Oct 5.

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

Author information

1
Transcriptome Bioinformatics, LIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany.
2
Interdisciplinary Center for Bioinformatics, University of Leipzig, Leipzig, Germany.
3
Bioinformatics Group, Department of Computer Science, University of Leipzig, Leipzig, Germany.
4
German ICGC MMML-Seq-project.
5
German Cancer Research Center (DKFZ), Division Molecular Genetics, Heidelberg, Germany.
6
Institute of Human Genetics, Christian-Albrechts-University, Kiel, Germany.
7
Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, Essen, Germany.
8
Department of Pediatrics, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
9
BLUEPRINT project.
10
Cell Networks, Bioquant, University of Heidelberg, Heidelberg, Germany.
11
Structural Biology and BioComputing Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain.
12
Deutsches Krebsforschungszentrum Heidelberg (DKFZ), Division Theoretical Bioinformatics, Heidelberg, Germany.
13
Department of Otorhinolaryngology, University of Duisburg-Essen, Essen, Germany.
14
University Hospital Muenster - Pediatric Hematology and Oncology, Münster Germany.
15
Leibniz-Institut DSMZ, German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany.
16
Department of Hematology and Oncology, Georg-Augusts-University of Göttingen, Göttingen, Germany.
17
Institute of Pharmacy and Molecular Biotechnology, Bioquant, University of Heidelberg, Heidelberg, Germany.
18
European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
19
Friedrich-Ebert Hospital Neumuenster, Clinics for Haematology, Oncology and Nephrology, Neumünster, Germany.
20
Institute of Pathology, Charité - University Medicine Berlin, Berlin, Germany.
21
Department of Internal Medicine II: Hematology and Oncology, University Medical Centre, Campus Kiel, Kiel, Germany.
22
Radboud University, Department of Molecular Biology, Faculty of Science, Nijmegen, Netherlands.
23
Hematopathology Section, Christian-Albrechts-University, Kiel, Germany.
24
Institute for Medical Informatics Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
25
Departamento de Anatomía Patológica, Farmacología y Microbiología, Universitat de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
26
Institute of Pathology, Medical Faculty of the Ulm University, Ulm, Germany.
27
University Hospital Giessen, Pediatric Hematology and Oncology, Giessen, Germany.
28
Institute of Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany.
29
RNomics Group, Fraunhofer Institute for Cell Therapy and Immunology IZI, Leipzig, Germany.
30
Santa Fe Institute, Santa Fe, New Mexico, United States of America.
31
Max-Planck-Institute for Mathematics in Sciences, Leipzig, Germany.
#
Contributed equally

Abstract

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.

PMID:
26437030
PMCID:
PMC5444523
DOI:
10.1038/ng.3413
[Indexed for MEDLINE]
Free PMC Article

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