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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 (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 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 Martin-Subero, J. I Articles by Siebert, R. Search for Related Content PubMed PubMed Citation Articles by Martin-Subero, J. I Articles by Siebert, R. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 18, 2008 Accepted November 30, 2008 New insights into the biology and origin of mature aggressive B-cell lymphomas by combined epigenomic, genomic and transcriptional profiling Jose I Martin-Subero, Markus Kreuz, Marina Bibikova, Stefan Bentink, Ole Ammerpohl, Eliza Wickham-Garcia, Maciej Rosolowski, Julia Richter, Lidia Lopez-Serra, Esteban Ballestar, Hilmar Berger, Xabier Agirre, Heinz-Wolfram Bernd, Vincenzo Calvanese, Sergio B Cogliatti, Hans G Drexler, Jian-Bing Fan, Mario F Fraga, Martin L Hansmann, Michael Hummel, Wolfram Klapper, Bernhard Korn, Ralf Kuppers, Roderick AF MacLeod, Peter Moller, German Ott, Christiane Pott, Felipe Prosper, Andreas Rosenwald, Carsten Schwaenen, Dirk Schubeler, Marc Seifert, Benjamin Sturzenhofecker, Michael Weber, Swen Wessendorf, Markus Loeffler, Lorenz Trumper, Harald Stein, Rainer Spang, Manel Esteller, David Barker, Dirk Hasenclever, and Reiner Siebert* Institute of Human Genetics, University Hospital Schleswig-Holstein Campus Kiel/Christian-Albrechts University, Kiel, Germany University of Leipzig, Leipzig, Germany Illumina Inc., San Diego, CA, United States University of Regensburg, Regensburg, Germany Spanish National Cancer Centre (CNIO), Madrid, Spain Clinica Universitaria, Universidad de Navarra, Pamplona, Spain University Hospital Schleswig-Holstein Campus Lubeck, Lubeck, Germany Kantonsspital St. Gallen, St. Gallen, Switzerland DSMZ-German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany University Hospital of Frankfurt, Frankfurt, Germany Campus Benjamin Franklin, Charite Universitatsmedizin Berlin, Berlin, Germany Institute of Hematopathology, University Hospital Schleswig-Holstein Campus Kiel/Christian-Albrechts University, Kiel, Germany German Cancer Research Center, Heidelberg, Germany University of Duisburg-Essen, Essen, Germany Institute of Pathology, University Hospital of Ulm, Ulm, Germany University of Wurzburg, Wurzburg, Germany Second Medical Department, University Hospital Schleswig-Holstein Campus Kiel/Christian-Albrechts University, Kiel, Germany Cytogenetic and Molecular Diagnostics, Internal Medicine III, University Hospital of Ulm, Ulm, Germany Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland Georg-August University of Gottingen, Gottingen, Germany * Corresponding author; email: rsiebert{at}medgen.uni-kiel.de. 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-NHL) characterized for their morphologic, genetic and transcriptional features, including molecular Burkitt lymphomas and diffuse large B-cell lymphomas. Hierarchical clustering indicated that methylation patterns in maB-NHL 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-NHL studied were expressed at low levels in lymphomas and normal hematopoietic tissues but not in non-hematopoietic tissues. These findings, especially the enrichment for polycomb targets in stem cells, indicate that maB-NHL with different morphological, genetic and transcriptional background share a similar stem cell-like epigenetic pattern. This suggests that maB-NHL 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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