title: DNA methylome analysis in Burkitt and follicular lymphomas identifies differentially methylated regions linked to somatic mutation and transcriptional control.
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.
authors.affiliation: Transcriptome Bioinformatics, LIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany.|Interdisciplinary Center for Bioinformatics, University of Leipzig, Leipzig, Germany.|Bioinformatics Group, Department of Computer Science, University of Leipzig, Leipzig, Germany.|German ICGC MMML-Seq-project.
authors.forename: Helene
authors.initials: H
authors.lastname: Kretzmer
authors.affiliation: Transcriptome Bioinformatics, LIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany.|Interdisciplinary Center for Bioinformatics, University of Leipzig, Leipzig, Germany.|Bioinformatics Group, Department of Computer Science, University of Leipzig, Leipzig, Germany.|German ICGC MMML-Seq-project.
authors.forename: Stephan H
authors.initials: SH
authors.lastname: Bernhart
authors.affiliation: German Cancer Research Center (DKFZ), Division Molecular Genetics, Heidelberg, Germany.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: German ICGC MMML-Seq-project.|Institute of Human Genetics, Christian-Albrechts-University, Kiel, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Haake
authors.affiliation: German ICGC MMML-Seq-project.|Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, Essen, Germany.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Weniger
authors.affiliation: Institute of Human Genetics, Christian-Albrechts-University, Kiel, Germany.|Department of Pediatrics, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.|BLUEPRINT project.
authors.forename: Anke K
authors.initials: AK
authors.lastname: Bergmann
authors.affiliation: Cell Networks, Bioquant, University of Heidelberg, Heidelberg, Germany.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Betts
authors.affiliation: BLUEPRINT project.|Structural Biology and BioComputing Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Carrillo-de-Santa-Pau
authors.affiliation: Transcriptome Bioinformatics, LIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany.|Interdisciplinary Center for Bioinformatics, University of Leipzig, Leipzig, Germany.|Bioinformatics Group, Department of Computer Science, University of Leipzig, Leipzig, Germany.|German ICGC MMML-Seq-project.
authors.forename: Gero
authors.initials: G
authors.lastname: Doose
authors.affiliation: Institute of Human Genetics, Christian-Albrechts-University, Kiel, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Gutwein
authors.affiliation: German ICGC MMML-Seq-project.|Institute of Human Genetics, Christian-Albrechts-University, Kiel, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Richter
authors.affiliation: German Cancer Research Center (DKFZ), Division Molecular Genetics, Heidelberg, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Hovestadt
authors.affiliation: Deutsches Krebsforschungszentrum Heidelberg (DKFZ), Division Theoretical Bioinformatics, Heidelberg, Germany.
authors.forename: Bingding
authors.initials: B
authors.lastname: Huang
authors.affiliation: BLUEPRINT project.|Structural Biology and BioComputing Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Rico
authors.affiliation: Transcriptome Bioinformatics, LIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany.|Interdisciplinary Center for Bioinformatics, University of Leipzig, Leipzig, Germany.|Bioinformatics Group, Department of Computer Science, University of Leipzig, Leipzig, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Jühling
authors.affiliation: Institute of Human Genetics, Christian-Albrechts-University, Kiel, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Kolarova
authors.affiliation: Cell Networks, Bioquant, University of Heidelberg, Heidelberg, Germany.
authors.forename: Qianhao
authors.initials: Q
authors.lastname: Lu
authors.affiliation: Transcriptome Bioinformatics, LIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany.|Interdisciplinary Center for Bioinformatics, University of Leipzig, Leipzig, Germany.|Bioinformatics Group, Department of Computer Science, University of Leipzig, Leipzig, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Otto
authors.affiliation: German ICGC MMML-Seq-project.|Institute of Human Genetics, Christian-Albrechts-University, Kiel, Germany.
authors.forename: Rabea
authors.initials: R
authors.lastname: Wagener
authors.affiliation: Department of Otorhinolaryngology, University of Duisburg-Essen, Essen, Germany.
authors.forename: Judith
authors.initials: J
authors.lastname: Arnolds
authors.affiliation: German ICGC MMML-Seq-project.|University Hospital Muenster - Pediatric Hematology and Oncology, Münster Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Burkhardt
authors.affiliation: German ICGC MMML-Seq-project.|Department of Pediatrics, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Claviez
authors.affiliation: Leibniz-Institut DSMZ, German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany.
authors.forename: Hans G
authors.initials: HG
authors.lastname: Drexler
authors.affiliation: German ICGC MMML-Seq-project.|Leibniz-Institut DSMZ, German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany.|Department of Hematology and Oncology, Georg-Augusts-University of Göttingen, Göttingen, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Eberth
authors.affiliation: German ICGC MMML-Seq-project.|Deutsches Krebsforschungszentrum Heidelberg (DKFZ), Division Theoretical Bioinformatics, Heidelberg, Germany.|Institute of Pharmacy and Molecular Biotechnology, Bioquant, University of Heidelberg, Heidelberg, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Eils
authors.affiliation: BLUEPRINT project.|European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Flicek
authors.affiliation: German ICGC MMML-Seq-project.|Friedrich-Ebert Hospital Neumuenster, Clinics for Haematology, Oncology and Nephrology, Neumünster, Germany.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Haas
authors.affiliation: German ICGC MMML-Seq-project.|Institute of Pathology, Charité - University Medicine Berlin, Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Humme
authors.affiliation: German ICGC MMML-Seq-project.|Department of Internal Medicine II: Hematology and Oncology, University Medical Centre, Campus Kiel, Kiel, Germany.
authors.forename: Dennis
authors.initials: D
authors.lastname: Karsch
authors.affiliation: BLUEPRINT project.|Radboud University, Department of Molecular Biology, Faculty of Science, Nijmegen, Netherlands.
authors.forename: Hinrik H D
authors.initials: HHD
authors.lastname: Kerstens
authors.affiliation: German ICGC MMML-Seq-project.|Hematopathology Section, Christian-Albrechts-University, Kiel, Germany.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Klapper
authors.affiliation: German ICGC MMML-Seq-project.|BLUEPRINT project.|Institute for Medical Informatics Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Kreuz
authors.affiliation: German ICGC MMML-Seq-project.|Deutsches Krebsforschungszentrum Heidelberg (DKFZ), Division Theoretical Bioinformatics, Heidelberg, Germany.
authors.forename: Chris
authors.initials: C
authors.lastname: Lawerenz
authors.affiliation: German ICGC MMML-Seq-project.|Institute of Pathology, Charité - University Medicine Berlin, Berlin, Germany.
authors.forename: Dido
authors.initials: D
authors.lastname: Lenzek
authors.affiliation: German ICGC MMML-Seq-project.|BLUEPRINT project.|Institute for Medical Informatics Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Loeffler
authors.affiliation: German ICGC MMML-Seq-project.|Institute of Human Genetics, Christian-Albrechts-University, Kiel, Germany.
authors.forename: Cristina
authors.initials: C
authors.lastname: López
authors.affiliation: Leibniz-Institut DSMZ, German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany.
authors.forename: Roderick A F
authors.initials: RAF
authors.lastname: MacLeod
authors.affiliation: BLUEPRINT project.|Radboud University, Department of Molecular Biology, Faculty of Science, Nijmegen, Netherlands.
authors.forename: Joost H A
authors.initials: JHA
authors.lastname: Martens
authors.affiliation: BLUEPRINT project.|Radboud University, Department of Molecular Biology, Faculty of Science, Nijmegen, Netherlands.
authors.forename: Marta
authors.initials: M
authors.lastname: Kulis
authors.affiliation: BLUEPRINT project.|Departamento de Anatomía Patológica, Farmacología y Microbiología, Universitat de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: José Ignacio
authors.initials: JI
authors.lastname: Martín-Subero
authors.affiliation: German ICGC MMML-Seq-project.|Institute of Pathology, Medical Faculty of the Ulm University, Ulm, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Möller
authors.affiliation: German ICGC MMML-Seq-project.|Institute of Human Genetics, Christian-Albrechts-University, Kiel, Germany.
authors.forename: Inga
authors.initials: I
authors.lastname: Nage
authors.affiliation: German Cancer Research Center (DKFZ), Division Molecular Genetics, Heidelberg, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Picelli
authors.affiliation: German ICGC MMML-Seq-project.|Institute of Human Genetics, Christian-Albrechts-University, Kiel, Germany.
authors.forename: Inga
authors.initials: I
authors.lastname: Vater
authors.affiliation: German ICGC MMML-Seq-project.|University Hospital Giessen, Pediatric Hematology and Oncology, Giessen, Germany.
authors.forename: Marius
authors.initials: M
authors.lastname: Rohde
authors.affiliation: German ICGC MMML-Seq-project.|Institute of Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany.
authors.forename: Philip
authors.initials: P
authors.lastname: Rosenstiel
authors.affiliation: German ICGC MMML-Seq-project.|Institute for Medical Informatics Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
authors.forename: Maciej
authors.initials: M
authors.lastname: Rosolowski
authors.affiliation: Cell Networks, Bioquant, University of Heidelberg, Heidelberg, Germany.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Russell
authors.affiliation: German ICGC MMML-Seq-project.|Institute of Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Schilhabel
authors.affiliation: German ICGC MMML-Seq-project.|Deutsches Krebsforschungszentrum Heidelberg (DKFZ), Division Theoretical Bioinformatics, Heidelberg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Schlesner
authors.affiliation: Transcriptome Bioinformatics, LIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany.|Interdisciplinary Center for Bioinformatics, University of Leipzig, Leipzig, Germany.|Bioinformatics Group, Department of Computer Science, University of Leipzig, Leipzig, Germany.|German ICGC MMML-Seq-project.|RNomics Group, Fraunhofer Institute for Cell Therapy and Immunology IZI, Leipzig, Germany.|Santa Fe Institute, Santa Fe, New Mexico, United States of America.|Max-Planck-Institute for Mathematics in Sciences, Leipzig, Germany.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Stadler
authors.affiliation: German ICGC MMML-Seq-project.
authors.forename: Monika
authors.initials: M
authors.lastname: Szczepanowski
authors.affiliation: German ICGC MMML-Seq-project.|Department of Hematology and Oncology, Georg-Augusts-University of Göttingen, Göttingen, Germany.
authors.forename: Lorenz
authors.initials: L
authors.lastname: Trümper
authors.affiliation: BLUEPRINT project.|Radboud University, Department of Molecular Biology, Faculty of Science, Nijmegen, Netherlands.
authors.forename: Hendrik G
authors.initials: HG
authors.lastname: Stunnenberg
authors.affiliation: German ICGC MMML-Seq-project.|Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, Essen, Germany.|BLUEPRINT project.
authors.forename: Ralf
authors.initials: R
authors.lastname: Küppers
authors.affiliation: German ICGC MMML-Seq-project.|Institute of Human Genetics, Christian-Albrechts-University, Kiel, Germany.
authors.forename: Ole
authors.initials: O
authors.lastname: Ammerpohl
authors.affiliation: German ICGC MMML-Seq-project.|German Cancer Research Center (DKFZ), Division Molecular Genetics, Heidelberg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Lichter
authors.affiliation: German ICGC MMML-Seq-project.|Institute of Human Genetics, Christian-Albrechts-University, Kiel, Germany.|BLUEPRINT project.
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
authors.affiliation: Transcriptome Bioinformatics, LIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany.|Interdisciplinary Center for Bioinformatics, University of Leipzig, Leipzig, Germany.|Bioinformatics Group, Department of Computer Science, University of Leipzig, Leipzig, Germany.|German ICGC MMML-Seq-project.|BLUEPRINT project.
authors.forename: Steve
authors.initials: S
authors.lastname: Hoffmann
authors.affiliation: German ICGC MMML-Seq-project.|German Cancer Research Center (DKFZ), Division Molecular Genetics, Heidelberg, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Radlwimmer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000378:metabolism; D002051:Burkitt Lymphoma / Q000235:genetics*; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D019175:DNA Methylation; D005260:Female; D015894:Genome, Human / Q000235:genetics; D018858:Germinal Center / Q000378:metabolism; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D008224:Lymphoma, Follicular / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D059467:Transcriptome / Q000235:genetics*; D014178:Translocation, Genetic; D055815:Young Adult
chemical_list: C489427:MYC protein, human; D015514:Oncogene Proteins, Fusion; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc