Martin-Subero, Jose I, Kreuz, Markus, Bibikova, Marina, Bentink, Stefan, Ammerpohl, Ole, Wickham-Garcia, Eliza, Rosolowski, Maciej, Richter, Julia, Lopez-Serra, Lidia, Ballestar, Esteban, Berger, Hilmar, Agirre, Xabier, Bernd, Heinz-Wolfram, Calvanese, Vincenzo, Cogliatti, Sergio B, Drexler, Hans G, Fan, Jian-Bing, Fraga, Mario F, Hansmann, Martin L, Hummel, Michael, Klapper, Wolfram, Korn, Bernhard, Kueppers, Ralf, Macleod, Roderick A F, Moeller, Peter, Ott, German, Pott, Christiane, Prosper, Felipe, Rosenwald, Andreas, Schwaenen, Carsten, Schuebeler, Dirk, Seifert, Marc, Stuerzenhofecker, Benjamin, Weber, Michel, Wessendorf, Swen, Loeffler, Markus, Truemper, Lorenz, Stein, Harald, Spang, Rainer, Esteller, Manel, Barker, David, 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
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez...
Additional Information:	author can archive post-print (ie final draft post-refereeing); On author's personal web site or On departmental web site
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez...
Date Deposited:	14 Dec 2009 13:50
Last Modified:	31 Jan 2013 01:02
URI:	https://oak.novartis.com/id/eprint/957