New insights into the biology and origin of mature aggressive B-cell lymphomas by combined epigenomic, genomic, and transcriptional profiling
| Autor: | José I, Martín-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, Küppers, Roderick A F, Macleod, Peter, Möller, German, Ott, Christiane, Pott, Felipe, Prosper, Andreas, Rosenwald, Carsten, Schwaenen, Dirk, Schübeler, Marc, Seifert, Benjamin, Stürzenhofecker, Michael, Weber, Swen, Wessendorf, Markus, Loeffler, Lorenz, Trümper, Harald, Stein, Rainer, Spang, Manel, Esteller, David, Barker, Dirk, Hasenclever, Reiner, Siebert, Maren, Wehner |
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| Přispěvatelé: | Biotechnologie et signalisation cellulaire (BSC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS), for the Molecular Mechanisms in Malignant Lymphomas Network Project of the Deutsche Krebshilfe |
| Rok vydání: | 2009 |
| Předmět: |
Male
Lymphoma B-Cell Transcription Genetic Immunology Biology Biochemistry Epigenesis Genetic 03 medical and health sciences 0302 clinical medicine immune system diseases hemic and lymphatic diseases Tumor Cells Cultured medicine Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Neoplasm Invasiveness Epigenetics Embryonic Stem Cells B cell Oligonucleotide Array Sequence Analysis 030304 developmental biology Epigenomics Genetics 0303 health sciences Gene Expression Profiling Genomics Cell Biology Hematology DNA Methylation Hematopoietic Stem Cells medicine.disease Lymphoma Gene Expression Regulation Neoplastic Cell Transformation Neoplastic medicine.anatomical_structure 030220 oncology & carcinogenesis DNA methylation Cancer research Female Stem cell Burkitt's lymphoma Diffuse large B-cell lymphoma Ciencias de la Salud::Oncología [Materias Investigacion] |
| Zdroj: | Blood Blood, American Society of Hematology, 2009, 113 (11), pp.2488-2497. ⟨10.1182/blood-2008-04-152900⟩ |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2008-04-152900 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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