Genomic and transcriptomic changes complement each other in the pathogenesis of sporadic Burkitt lymphoma.

Adolescent Alternative Splicing / genetics Amino Acid Sequence Basic Helix-Loop-Helix Transcription Factors / chemistry Burkitt Lymphoma / genetics Child Child, Preschool Chromosome Breakpoints Cohort Studies DNA Methylation / genetics DNA Mutational Analysis Female Gene Expression Profiling Gene Expression Regulation, Neoplastic Genome, Human Humans INDEL Mutation / genetics Male Oncogene Proteins, Fusion / genetics Open Reading Frames / genetics Polymorphism, Single Nucleotide / genetics Proto-Oncogene Proteins c-myc / genetics Transcriptome / genetics Translocation, Genetic Whole Genome Sequencing

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
29 03 2019
Historique:
received: 21 08 2018
accepted: 18 01 2019
entrez: 31 3 2019
pubmed: 31 3 2019
medline: 6 5 2019
Statut: epublish

Résumé

Burkitt lymphoma (BL) is the most common B-cell lymphoma in children. Within the International Cancer Genome Consortium (ICGC), we performed whole genome and transcriptome sequencing of 39 sporadic BL. Here, we unravel interaction of structural, mutational, and transcriptional changes, which contribute to MYC oncogene dysregulation together with the pathognomonic IG-MYC translocation. Moreover, by mapping IGH translocation breakpoints, we provide evidence that the precursor of at least a subset of BL is a B-cell poised to express IGHA. We describe the landscape of mutations, structural variants, and mutational processes, and identified a series of driver genes in the pathogenesis of BL, which can be targeted by various mechanisms, including IG-non MYC translocations, germline and somatic mutations, fusion transcripts, and alternative splicing.

Identifiants

DOI: 10.1038/s41467-019-08578-3 PMID: 30926794 PMC: PMC6440956
pubmed: 30926794
doi: 10.1038/s41467-019-08578-3
pii: 10.1038/s41467-019-08578-3
pmc: PMC6440956
doi:

Substances chimiques

Basic Helix-Loop-Helix Transcription Factors 0
Oncogene Proteins, Fusion 0
Proto-Oncogene Proteins c-myc 0
TCF3 protein, human 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1459

Investigateurs

Susanne Wagner (S)
Gesine Richter (G)
Jürgen Eils (J)
Jules Kerssemakers (J)
Christina Jaeger-Schmidt (C)
Ingrid Scholz (I)
Christoph Borst (C)
Friederike Braulke (F)
Martin Dreyling (M)
Sonja Eberth (S)
Hermann Einsele (H)
Norbert Frickhofen (N)
Siegfried Haas (S)
Dennis Karsch (D)
Nicole Klepl (N)
Michael Kneba (M)
Jasmin Lisfeld (J)
Luisa Mantovani-Löffler (L)
German Ott (G)
Christina Stadler (C)
Peter Staib (P)
Thorsten Zenz (T)
Dieter Kube (D)
Ulrike Kostezka (U)
Vera Binder (V)
Ellen Leich (E)
Inga Nagel (I)
Jordan Pischimariov (J)
Stefan Schreiber (S)
Inga Vater (I)
Lydia Hopp (L)
David Langenberger (D)
Maciej Rosolowski (M)

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Auteurs

Cristina López (C)

Institute of Human Genetics, Ulm University and Ulm University Medical Center, 89081, Ulm, Germany.
Institute of Human Genetics, Christian-Albrechts-University, 24105, Kiel, Germany.
ORCID: 0000-0001-6644-1659

Kortine Kleinheinz (K)

Division of Theoretical Bioinformatics (B080), German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
Department for Bioinformatics and Functional Genomics, Institute of Pharmacy and Molecular Biotechnology and Bioquant, University of Heidelberg, 69120, Heidelberg, Germany.
ORCID: 0000-0002-1859-2281

Sietse M Aukema (SM)

Institute of Human Genetics, Christian-Albrechts-University, 24105, Kiel, Germany.
Hematopathology Section, Christian-Albrechts-University, 24105, Kiel, Germany.

Marius Rohde (M)

Pediatric Hematology and Oncology, University Hospital Giessen, 35392, Giessen, Germany.

Stephan H Bernhart (SH)

Interdisciplinary Center for Bioinformatics, University of Leipzig, 04107, Leipzig, Germany.
Bioinformatics Group, Department of Computer, University of Leipzig, 04107, Leipzig, Germany.
Transcriptome Bioinformatics, LIFE Research Center for Civilization Diseases, University of Leipzig, 04107, Leipzig, Germany.

Daniel Hübschmann (D)

Division of Theoretical Bioinformatics (B080), German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
Department of Pediatric Immunology, Hematology and Oncology, University Hospital, 69120, Heidelberg, Germany.
German Cancer Research Center (DKFZ), Division of Stem Cells and Cancer, Heidelberg, Germany and Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120, Heidelberg, Germany.

Rabea Wagener (R)

Institute of Human Genetics, Ulm University and Ulm University Medical Center, 89081, Ulm, Germany.
Institute of Human Genetics, Christian-Albrechts-University, 24105, Kiel, Germany.

Umut H Toprak (UH)

Division of Theoretical Bioinformatics (B080), German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
Bioinformatics and Omics Data Analytics (B240), German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
Faculty of Biosciences, Heidelberg University, 69120, Heidelberg, Germany.

Francesco Raimondi (F)

Cell Networks, Bioquant and Biochemistry CenterBiochemie Zentrum Heidelberg (BZH), University of Heidelberg, 69120, Heidelberg, Germany.

Markus Kreuz (M)

Institute for Medical Informatics Statistics and Epidemiology, 04107, Leipzig, Germany.

Sebastian M Waszak (SM)

Genome Biology Unit, EMBL Heidelberg, 69117, Heidelberg, Germany.
ORCID: 0000-0003-3042-9521

Zhiqin Huang (Z)

Division of Molecular Genetics, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.

Lina Sieverling (L)

Faculty of Biosciences, Heidelberg University, 69120, Heidelberg, Germany.
Division of Applied Bioinformatics (G200), German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.

Nagarajan Paramasivam (N)

Division of Theoretical Bioinformatics (B080), German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
Medical Faculty Heidelberg, Heidelberg University, 69120, Heidelber, Germany.

Julian Seufert (J)

Bioinformatics and Omics Data Analytics (B240), German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.

Stephanie Sungalee (S)

Genome Biology Unit, EMBL Heidelberg, 69117, Heidelberg, Germany.
ORCID: 0000-0001-5633-8826

Robert B Russell (RB)

Cell Networks, Bioquant and Biochemistry CenterBiochemie Zentrum Heidelberg (BZH), University of Heidelberg, 69120, Heidelberg, Germany.
ORCID: 0000-0002-1905-4717

Julia Bausinger (J)

Institute of Human Genetics, Ulm University and Ulm University Medical Center, 89081, Ulm, Germany.

Helene Kretzmer (H)

Interdisciplinary Center for Bioinformatics, University of Leipzig, 04107, Leipzig, Germany.
Bioinformatics Group, Department of Computer, University of Leipzig, 04107, Leipzig, Germany.
Transcriptome Bioinformatics, LIFE Research Center for Civilization Diseases, University of Leipzig, 04107, Leipzig, Germany.
Department of Genome Regulation, Max Planck Institute for Molecular Genetics, 14195, Berlin, Germany.

Ole Ammerpohl (O)

Institute of Human Genetics, Ulm University and Ulm University Medical Center, 89081, Ulm, Germany.

Anke K Bergmann (AK)

Institute of Human Genetics, Christian-Albrechts-University, 24105, Kiel, Germany.
Department of Pediatrics, University Hospital Schleswig-Holstein, Campus Kiel, 24105, Kiel, Germany.

Hans Binder (H)

Interdisciplinary Center for Bioinformatics, University of Leipzig, 04107, Leipzig, Germany.
Bioinformatics Group, Department of Computer, University of Leipzig, 04107, Leipzig, Germany.

Arndt Borkhardt (A)

Medical Faculty, Department of Pediatric Oncology, Hematology and Clinical Immunology, Heinrich-Heine-University, 40225, Düsseldorf, Germany.
ORCID: 0000-0002-6121-4737

Benedikt Brors (B)

Division of Applied Bioinformatics (G200), German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
ORCID: 0000-0001-5940-3101

Alexander Claviez (A)

Department of Pediatrics, University Hospital Schleswig-Holstein, Campus Kiel, 24105, Kiel, Germany.

Gero Doose (G)

Interdisciplinary Center for Bioinformatics, University of Leipzig, 04107, Leipzig, Germany.
Bioinformatics Group, Department of Computer, University of Leipzig, 04107, Leipzig, Germany.
Transcriptome Bioinformatics, LIFE Research Center for Civilization Diseases, University of Leipzig, 04107, Leipzig, Germany.

Lars Feuerbach (L)

Division of Applied Bioinformatics (G200), German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.

Andrea Haake (A)

Institute of Human Genetics, Christian-Albrechts-University, 24105, Kiel, Germany.

Martin-Leo Hansmann (ML)

Senckenberg Institute of Pathology, University of Frankfurt Medical School, 60590, Frankfurt am Main, Germany.

Jessica Hoell (J)

Medical Faculty, Department of Pediatric Oncology, Hematology and Clinical Immunology, Heinrich-Heine-University, 40225, Düsseldorf, Germany.

Michael Hummel (M)

Institute of Pathology, Charité - University Medicine Berlin, 10117, Berlin, Germany.

Jan O Korbel (JO)

Genome Biology Unit, EMBL Heidelberg, 69117, Heidelberg, Germany.
ORCID: 0000-0002-2798-3794

Chris Lawerenz (C)

Division of Theoretical Bioinformatics (B080), German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.

Dido Lenze (D)

Institute of Pathology, Charité - University Medicine Berlin, 10117, Berlin, Germany.

Bernhard Radlwimmer (B)

Division of Molecular Genetics, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.

Julia Richter (J)

Institute of Human Genetics, Christian-Albrechts-University, 24105, Kiel, Germany.
Hematopathology Section, Christian-Albrechts-University, 24105, Kiel, Germany.
ORCID: 0000-0002-9543-4084

Philip Rosenstiel (P)

Institute of Clinical Molecular Biology, Christian-Albrechts-University, 24105, Kiel, Germany.

Andreas Rosenwald (A)

Institute of Pathology, Comprehensive Cancer Center Mainfranken, University of Würzburg, 97080, Würzburg, Germany.

Markus B Schilhabel (MB)

Institute of Clinical Molecular Biology, Christian-Albrechts-University, 24105, Kiel, Germany.

Harald Stein (H)

Pathodiagnostik Berlin, 12099, Berlin, Germany.

Stephan Stilgenbauer (S)

Department for Internal Medicine III, Ulm University, 89081, Ulm, Germany.

Peter F Stadler (PF)

Bioinformatics Group, Department of Computer, University of Leipzig, 04107, Leipzig, Germany.
ORCID: 0000-0002-5016-5191

Monika Szczepanowski (M)

Hematopathology Section, Christian-Albrechts-University, 24105, Kiel, Germany.

Marc A Weniger (MA)

Institute of Cell Biology (Cancer Research), Medical School, University of Duisburg-Essen, 45147, Essen, Germany.

Marc Zapatka (M)

Division of Molecular Genetics, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
ORCID: 0000-0001-8287-5967

Roland Eils (R)

Division of Theoretical Bioinformatics (B080), German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
Department for Bioinformatics and Functional Genomics, Institute of Pharmacy and Molecular Biotechnology and Bioquant, University of Heidelberg, 69120, Heidelberg, Germany.
ORCID: 0000-0002-0034-4036

Peter Lichter (P)

Division of Molecular Genetics, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.

Markus Loeffler (M)

Institute for Medical Informatics Statistics and Epidemiology, 04107, Leipzig, Germany.

Peter Möller (P)

Institute of Pathology, University of Ulm and University Hospital of Ulm, 89081, Ulm, Germany.

Lorenz Trümper (L)

Department of Hematology and Oncology, Georg-August-University of Göttingen, 37075, Göttingen, Germany.

Wolfram Klapper (W)

Hematopathology Section, Christian-Albrechts-University, 24105, Kiel, Germany.

Steve Hoffmann (S)

Interdisciplinary Center for Bioinformatics, University of Leipzig, 04107, Leipzig, Germany.
Bioinformatics Group, Department of Computer, University of Leipzig, 04107, Leipzig, Germany.
Transcriptome Bioinformatics, LIFE Research Center for Civilization Diseases, University of Leipzig, 04107, Leipzig, Germany.
Computational Biology, Leibniz Institute on Ageing-Fritz Lipmann Institut (FLI), 07745, Jena, Germany.

Ralf Küppers (R)

Institute of Cell Biology (Cancer Research), Medical School, University of Duisburg-Essen, 45147, Essen, Germany.
ORCID: 0000-0002-6691-7191

Birgit Burkhardt (B)

University Hospital Münster - Pediatric Hematology and Oncology, 48149, Münster, Germany.

Matthias Schlesner (M)

Division of Theoretical Bioinformatics (B080), German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany. m.schlesner@Dkfz-Heidelberg.de.
Bioinformatics and Omics Data Analytics (B240), German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany. m.schlesner@Dkfz-Heidelberg.de.
ORCID: 0000-0002-5896-4086

Reiner Siebert (R)

Institute of Human Genetics, Ulm University and Ulm University Medical Center, 89081, Ulm, Germany. reiner.siebert@uni-ulm.de.
Institute of Human Genetics, Christian-Albrechts-University, 24105, Kiel, Germany. reiner.siebert@uni-ulm.de.

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adolescent › Genomic and transcriptomic changes complement...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Maturation post-transcriptionnelle des ARN › Épissage des ARN › Épissage alternatif › Genomic and transcriptomic changes complement...
questionsmedicales.fr › Sciences de l'information › Sources d'information › Services d'information › Documentation › Données de séquences moléculaires › Séquence d'acides aminés › Genomic and transcriptomic changes complement...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription à motif basique hélice-boucle-hélice › Genomic and transcriptomic changes complement...
questionsmedicales.fr › Maladies du système immunitaire › Syndromes immunoprolifératifs › Syndromes lymphoprolifératifs › Lymphomes › Lymphome malin non hodgkinien › Lymphome B › Lymphome de Burkitt › Genomic and transcriptomic changes complement...
questionsmedicales.fr › Personnes › Tranches d'âge › Enfant › Genomic and transcriptomic changes complement...
questionsmedicales.fr › Personnes › Tranches d'âge › Enfant › Enfant d'âge préscolaire › Genomic and transcriptomic changes complement...
questionsmedicales.fr › Phénomènes génétiques › Altération de l'ADN › Cassures de l'ADN › Points de cassure de chromosome › Genomic and transcriptomic changes complement...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Genomic and transcriptomic changes complement...
questionsmedicales.fr › Phénomènes génétiques › Méthylation de l'ADN › Genomic and transcriptomic changes complement...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Analyse de séquence d'ADN › Analyse de mutations d'ADN › Genomic and transcriptomic changes complement...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de profil d'expression de gènes › Genomic and transcriptomic changes complement...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Régulation de l'expression des gènes tumoraux › Genomic and transcriptomic changes complement...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Génome humain › Genomic and transcriptomic changes complement...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Genomic and transcriptomic changes complement...
questionsmedicales.fr › Phénomènes génétiques › Mutagenèse › Mutation de type INDEL › Genomic and transcriptomic changes complement...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines oncogènes › Protéines de fusion oncogènes › Genomic and transcriptomic changes complement...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Gènes › Composants de gène › Cadres ouverts de lecture › Genomic and transcriptomic changes complement...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Polymorphisme de nucléotide simple › Genomic and transcriptomic changes complement...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription à motif basique hélice-boucle-hélice › Protéines proto-oncogènes c-myc › Genomic and transcriptomic changes complement...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Transcriptome › Genomic and transcriptomic changes complement...
questionsmedicales.fr › Phénomènes génétiques › Mutagenèse › Translocation génétique › Genomic and transcriptomic changes complement...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Analyse de séquence d'ADN › Séquençage du génome entier › Genomic and transcriptomic changes complement...