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Nat Genet. 2015 Nov;47(11):1316-25. 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

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

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
[PubMed - indexed for MEDLINE]
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