A comprehensive microarray-based DNA methylation study of 367 hematological neoplasms
| Autor: | Lorenz Trümper, Sylvia Hartmann, Reiner Siebert, Eliza Wickham-Garcia, Julia Richter, Martin J. S. Dyer, Martin Dreyling, María José Calasanz, Marc Seifert, José I. Martín-Subero, Jian-Bing Fan, Harald Stein, Wolfram Klapper, Javier Suela, Ralf Küppers, Marina Bibikova, Martina Deckert, Jose Roman-Gomez, Jan Dürig, Inga Nagel, Stefanie Bug, Ole Ammerpohl, Christiane Pott, Inga Vater, Felipe Prosper, Monika Brüggemann, Juan C. Cigudosa, Ming Q. Du, Stefan Gesk, Claudia Haferlach, Manuel Montesinos-Rongen, Martin-Leo Hansmann, Sara Alvarez, Lana Harder, Xabier Agirre |
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| Přispěvatelé: | Universitat de Barcelona |
| Rok vydání: | 2009 |
| Předmět: |
Candidate gene
Myeloid T-Lymphocytes ADN lcsh:Medicine 0302 clinical medicine Cluster Analysis lcsh:Science Oncology/Hematological Malignancies Promoter Regions Genetic Oligonucleotide Array Sequence Analysis Genetics B-Lymphocytes/metabolism CpG Islands DNA Methylation Gene Expression Profiling Hematologic Neoplasms/genetics Hematologic Neoplasms/metabolism Humans Oligonucleotide Array Sequence Analysis/methods Promoter Regions Genetic T-Lymphocytes/metabolism 0303 health sciences B-Lymphocytes Multidisciplinary medicine.anatomical_structure CpG site Cèl·lules T 030220 oncology & carcinogenesis Hematologic Neoplasms DNA methylation Hematology/Lymphomas and Chronic Lymphoblastic Leukemia Ciencias de la Salud::Oncología [Materias Investigacion] Research Article Cèl·lules B T cells Biology 03 medical and health sciences Genetics and Genomics/Epigenetics medicine Epigenetics ddc:610 Gene Genetics and Genomics/Cancer Genetics 030304 developmental biology B cells lcsh:R Promoter DNA Expressió gènica Gene expression profiling Cancer research lcsh:Q Gene expression |
| Zdroj: | Dipòsit Digital de la UB Universidad de Barcelona PLoS ONE Recercat. Dipósit de la Recerca de Catalunya instname Dadun. Depósito Académico Digital de la Universidad de Navarra PLoS ONE, Vol 4, Iss 9, p e6986 (2009) |
| Popis: | Background: Alterations in the DNA methylation pattern are a hallmark of leukemias and lymphomas. However, most epigenetic studies in hematologic neoplasms (HNs) have focused either on the analysis of few candidate genes or many genes and few HN entities, and comprehensive studies are required. Methodology/Principal Findings: Here, we report for the first time a microarray-based DNA methylation study of 767 genes in 367 HNs diagnosed with 16 of the most representative B-cell (n = 203), T-cell (n = 30), and myeloid (n = 134) neoplasias, as well as 37 samples from different cell types of the hematopoietic system. Using appropriate controls of B-, T-, or myeloid cellular origin, we identified a total of 220 genes hypermethylated in at least one HN entity. In general, promoter hypermethylation was more frequent in lymphoid malignancies than in myeloid malignancies, being germinal center mature B-cell lymphomas as well as B and T precursor lymphoid neoplasias those entities with highest frequency of geneassociated DNA hypermethylation. We also observed a significant correlation between the number of hypermethylated and hypomethylated genes in several mature B-cell neoplasias, but not in precursor B- and T-cell leukemias. Most of the genes becoming hypermethylated contained promoters with high CpG content, and a significant fraction of them are targets of the polycomb repressor complex. Interestingly, T-cell prolymphocytic leukemias show low levels of DNA hypermethylation and a comparatively large number of hypomethylated genes, many of them showing an increased gene expression. Conclusions/Significance: We have characterized the DNA methylation profile of a wide range of different HNs entities. As well as identifying genes showing aberrant DNA methylation in certain HN subtypes, we also detected six genes—DBC1, DIO3, FZD9, HS3ST2, MOS, and MYOD1—that were significantly hypermethylated in B-cell, T-cell, and myeloid malignancies. These might therefore play an important role in the development of different HNs. |
| Databáze: | OpenAIRE |
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