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New insights into the biology and origin of mature aggressive B-cell lymphomas by combined epigenomic, genomic, and transcriptional profiling.

Martin-Subero, Jose I and Kreuz, Markus and Bibikova, Marina and Bentink, Stefan and Ammerpohl, Ole and Wickham-Garcia, Eliza and Rosolowski, Maciej and Richter, Julia and Lopez-Serra, Lidia and Ballestar, Esteban and Berger, Hilmar and Agirre, Xabier and Bernd, Heinz-Wolfram and Calvanese, Vincenzo and Cogliatti, Sergio B and Drexler, Hans G and Fan, Jian-Bing and Fraga, Mario F and Hansmann, Martin L and Hummel, Michael and Klapper, Wolfram and Korn, Bernhard and Kueppers, Ralf and Macleod, Roderick A F and Moeller, Peter and Ott, German and Pott, Christiane and Prosper, Felipe and Rosenwald, Andreas and Schwaenen, Carsten and Schuebeler, Dirk and Seifert, Marc and Stuerzenhofecker, Benjamin and Weber, Michel and Wessendorf, Swen and Loeffler, Markus and Truemper, Lorenz and Stein, Harald and Spang, Rainer and Esteller, Manel and Barker, David and Hasenclever, Dirk and Siebert, Reiner (2009) New insights into the biology and origin of mature aggressive B-cell lymphomas by combined epigenomic, genomic, and transcriptional profiling. Blood, 113 (11). pp. 2488-2497. ISSN 1528-0020

Abstract

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.

Item Type: Article
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Additional Information: author can archive post-print (ie final draft post-refereeing); On author's personal web site or On departmental web site
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Date Deposited: 14 Dec 2009 13:50
Last Modified: 31 Jan 2013 01:02
URI: https://oak.novartis.com/id/eprint/957

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