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Blood, 12 March 2009, Vol. 113, No. 11, pp. 2488-2497. Prepublished online as a Blood First Edition Paper on December 15, 2008; DOI 10.1182/blood-2008-04-152900. This Article Full Text Full Text (PDF) Supplemental Appendix, Methods, Tables, and Figures Additional Supplemental Figures All Versions of this Article: blood-2008-04-152900v1 113/11/2488    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Martín-Subero, J. I. Articles by Siebert, R. Search for Related Content PubMed PubMed Citation Articles by Martín-Subero, J. I. Articles by Siebert, R. Related Collections Lymphoid Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  LYMPHOID NEOPLASIA New insights into the biology and origin of mature aggressive B-cell lymphomas by combined epigenomic, genomic, and transcriptional profiling José I. Martín-Subero1,*, Markus Kreuz2,*, Marina Bibikova3,*, Stefan Bentink4,*, Ole Ammerpohl1, Eliza Wickham-Garcia3, Maciej Rosolowski2, Julia Richter1, Lidia Lopez-Serra5, Esteban Ballestar5, Hilmar Berger2, Xabier Agirre6, Heinz-Wolfram Bernd7, Vincenzo Calvanese5, Sergio B. Cogliatti8, Hans G. Drexler9, Jian-Bing Fan3, Mario F. Fraga5, Martin L. Hansmann10, Michael Hummel11, Wolfram Klapper12, Bernhard Korn13, Ralf Küppers14, Roderick A. F. MacLeod9, Peter Möller15, German Ott16, Christiane Pott17, Felipe Prosper6, Andreas Rosenwald16, Carsten Schwaenen18, Dirk Schübeler19, Marc Seifert14, Benjamin Stürzenhofecker20, Michael Weber19, Swen Wessendorf18, Markus Loeffler2, Lorenz Trümper20, Harald Stein11, Rainer Spang4, Manel Esteller5, David Barker3, Dirk Hasenclever2, for the Molecular Mechanisms in Malignant Lymphomas Network Project of the Deutsche Krebshilfe, and Reiner Siebert1 1 Institute of Human Genetics, University Hospital Schleswig-Holstein Campus Kiel/Christian-Albrechts University Kiel, Kiel, Germany; 2 Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany; 3 Illumina, San Diego, CA; 4 Institute of Functional Genomics, University of Regensburg, Regensburg, Germany; 5 Cancer Epigenetics Laboratory, Spanish National Cancer Centre (CNIO), Madrid, Spain; 6 Foundation for Applied Medical Research, Division of Cancer and Area of Cell Therapy and Hematology Service, Clínica Universitaria, Universidad de Navarra, Pamplona, Spain; 7 Institute of Pathology, University Hospital Schleswig-Holstein Campus Lübeck, Lübeck, Germany; 8 Institute of Pathology, Kantonsspital St Gallen, St Gallen, Switzerland; 9 DSMZ-German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany; 10 Institute of Pathology, University Hospital of Frankfurt, Frankfurt, Germany; 11 Institute of Pathology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Berlin, Germany; 12 Institute of Hematopathology, University Hospital Schleswig-Holstein Campus Kiel/Christian-Albrechts University Kiel, Kiel, Germany; 13 Genomics and Proteomics Core Facility, German Cancer Research Center, Heidelberg, Germany; 14 Institute for Cell Biology (Tumor Research), University of Duisburg-Essen, Essen, Germany; 15 Institute of Pathology, University Hospital of Ulm, Ulm, Germany; 16 Institute of Pathology, University of Würzburg, Würzburg, Germany; 17 Second Medical Department, University Hospital Schleswig-Holstein Campus Kiel/Christian-Albrechts University Kiel, Kiel, Germany; 18 Cytogenetic and Molecular Diagnostics, Internal Medicine III, University Hospital of Ulm, Ulm, Germany; 19 Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland; and 20 Department of Hematology and Oncology, Georg-August University of Göttingen, Göttingen, Germany Lymphomas are assumed to originate at different stages of lymphocyte development through chromosomal aberrations. Thus, different lymphomas resemble lymphocytes at distinct differentiation stages and show characteristic morphologic, genetic, and transcriptional features. Here, we have performed a microarray-based DNA methylation profiling of 83 mature aggressive B-cell non-Hodgkin lymphomas (maB-NHLs) characterized for their morphologic, genetic, and transcriptional features, including molecular Burkitt lymphomas and diffuse large B-cell lymphomas. Hierarchic clustering indicated that methylation patterns in maB-NHLs were not strictly associated with morphologic, genetic, or transcriptional features. By supervised analyses, we identified 56 genes de novo methylated in all lymphoma subtypes studied and 22 methylated in a lymphoma subtype–specific manner. Remarkably, the group of genes de novo methylated in all lymphoma subtypes was significantly enriched for polycomb targets in embryonic stem cells. De novo methylated genes in all maB-NHLs studied were expressed at low levels in lymphomas and normal hematopoietic tissues but not in nonhematopoietic tissues. These findings, especially the enrichment for polycomb targets in stem cells, indicate that maB-NHLs with different morphologic, genetic, and transcriptional background share a similar stem cell–like epigenetic pattern. This suggests that maB-NHLs originate from cells with stem cell features or that stemness was acquired during lymphomagenesis by epigenetic remodeling. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. Carlotti and J. G. Gribben Stem cell mimicry: key to transformation? Blood, October 8, 2009; 114(15): 3133 - 3134. [Abstract] [Full Text] [PDF] A. J. Gentles, A. A. Alizadeh, S.-I. Lee, J. H. Myklebust, C. M. Shachaf, B. Shahbaba, R. Levy, D. Koller, and S. K. Plevritis A pluripotency signature predicts histologic transformation and influences survival in follicular lymphoma patients Blood, October 8, 2009; 114(15): 3158 - 3166. [Abstract] [Full Text] [PDF]

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