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

@article{citeulike:3823774, 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-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.}, author = {Martin-Subero, Jose I 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 W. and Calvanese, Vincenzo and Cogliatti, Sergio B B. and Drexler, Hans G G. and Fan, Jian-Bing B. and Fraga, Mario F F. and Hansmann, Martin L L. and Hummel, Michael and Klapper, Wolfram and Korn, Bernhard and Kuppers, Ralf and Macleod, Roderick Af A. and Moller, Peter and Ott, German and Pott, Christiane and Prosper, Felipe and Rosenwald, Andreas and Schwaenen, Carsten and Schubeler, Dirk and Seifert, Marc and Sturzenhofecker, Benjamin and Weber, Michael and Wessendorf, Swen and Loeffler, Markus and Trumper, Lorenz and Stein, Harald and Spang, Rainer and Esteller, Manel and Barker, David and Hasenclever, Dirk and Siebert, Reiner}, citeulike-article-id = {3823774}, citeulike-linkout-0 = {http://dx.doi.org/10.1182/blood-2008-04-152900}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19075189}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19075189}, doi = {10.1182/blood-2008-04-152900}, issn = {1528-0020}, journal = {Blood}, keywords = {dlbcl, methylation}, month = {December}, posted-at = {2008-12-25 18:22:31}, priority = {2}, title = {New insights into the biology and origin of mature aggressive B-cell lymphomas by combined epigenomic, genomic and transcriptional profiling.}, url = {http://dx.doi.org/10.1182/blood-2008-04-152900}, year = {2008} }

TY - JOUR ID - citeulike:3823774 L3 - citeulike-article-id:3823774 N2 - 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. JF - Blood SN - 1528-0020 TI - New insights into the biology and origin of mature aggressive B-cell lymphomas by combined epigenomic, genomic and transcriptional profiling. KW - dlbcl KW - methylation AU - Martin-Subero, Jose I AU - Kreuz, Markus AU - Bibikova, Marina AU - Bentink, Stefan AU - Ammerpohl, Ole AU - Wickham-Garcia, Eliza AU - Rosolowski, Maciej AU - Richter, Julia AU - Lopez-Serra, Lidia AU - Ballestar, Esteban AU - Berger, Hilmar AU - Agirre, Xabier AU - Bernd, Heinz-Wolfram AU - Calvanese, Vincenzo AU - Cogliatti, Sergio B AU - Drexler, Hans G AU - Fan, Jian-Bing AU - Fraga, Mario F AU - Hansmann, Martin L AU - Hummel, Michael AU - Klapper, Wolfram AU - Korn, Bernhard AU - Kuppers, Ralf AU - Macleod, Roderick Af AU - Moller, Peter AU - Ott, German AU - Pott, Christiane AU - Prosper, Felipe AU - Rosenwald, Andreas AU - Schwaenen, Carsten AU - Schubeler, Dirk AU - Seifert, Marc AU - Sturzenhofecker, Benjamin AU - Weber, Michael AU - Wessendorf, Swen AU - Loeffler, Markus AU - Trumper, Lorenz AU - Stein, Harald AU - Spang, Rainer AU - Esteller, Manel AU - Barker, David AU - Hasenclever, Dirk AU - Siebert, Reiner PY - 2008/12/15/ UR - http://dx.doi.org/10.1182/blood-2008-04-152900 ER -