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

Publication

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

Journal Paper/Review - Mar 12, 2009

Molecular Mechanisms in Malignant Lymphomas Network Project of the Deutsche Krebshilfe, Seifert Marc, Schübeler Dirk, Schwaenen Carsten, Rosenwald Andreas, Prosper Felipe, Pott Christiane, Ott German, Möller Peter, Macleod Roderick A F, Stürzenhofecker Benjamin, Weber Michael, Siebert Reiner, Hasenclever Dirk, Barker David, Esteller Manel, Spang Rainer, Stein Harald, Trümper Lorenz, Loeffler Markus, Wessendorf Swen, Küppers Ralf, Korn Bernhard, Ballestar Esteban, Lopez-Serra Lidia, Richter Julia, Rosolowski Maciej, Wickham-Garcia Eliza, Ammerpohl Ole, Bentink Stefan, Bibikova Marina, Kreuz Markus, Berger Hilmar, Agirre Xabier, Klapper Wolfram, Hummel Michael, Hansmann Martin L, Fraga Mario F, Fan Jian-Bing, Drexler Hans G, Cogliatti Sergio B., Calvanese Vincenzo, Bernd Heinz-Wolfram, Martín-Subero José I

Citation

Molecular Mechanisms in Malignant Lymphomas Network Project of the Deutsche Krebshilfe, Seifert M, Schübeler D, Schwaenen C, Rosenwald A, Prosper F, Pott C, Ott G, Möller P, Macleod R, Stürzenhofecker B, Weber M, Siebert R, Hasenclever D, Barker D, Esteller M, Spang R, Stein H, Trümper L, Loeffler M, Wessendorf S, Küppers R, Korn B, Ballestar E, Lopez-Serra L, Richter J, Rosolowski M, Wickham-Garcia E, Ammerpohl O, Bentink S, Bibikova M, Kreuz M, Berger H, Agirre X, Klapper W, Hummel M, Hansmann M, Fraga M, Fan J, Drexler H, Cogliatti S, Calvanese V, Bernd H, Martín-Subero J. New insights into the biology and origin of mature aggressive B-cell lymphomas by combined epigenomic, genomic, and transcriptional profiling. Blood 2009; 113:2488-97.

Type

Journal Paper/Review (English)

Journal

Blood 2009; 113

Publication Date

Mar 12, 2009

Issn Electronic

1528-0020

Pages

2488-97

Brief description/objective

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.