A comprehensive microarray-based DNA methylation study of 367 hematological neoplasms

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
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 gene-associated 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.
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Author:Jose Ignacio Martin-Subero, Ole Ammerpohl, Marina Bibikova, Eliza Wickham-Garcia, Xabier Agirre, Sara Alvarez, Monika Brüggemann, Stefanie Bug, Maria J. Calasanz, Martina Deckert, Martin Dreyling, Ming Q. Du, Jan Dürig, Martin J. S. Dyer, Jian-Bing Fan, Stefan Gesk, Martin-Leo Hansmann, Lana Harder, Sylvia Hartmann, Wolfram Klapper, Ralf Küppers, Manuel Montesinos-Rongen, Inga Nagel, Christiane Pott, Julia Richter, José Román-Gómez, Marc Seifert, Harald Stein, Javier Suela, Lorenz Trümper, Inga Vater, Felipe Prosper, Claudia Haferlach, Juan Cruz Cigudosa, Reiner Siebert
URN:urn:nbn:de:hebis:30-115114
DOI:http://dx.doi.org/10.1371/journal.pone.0006986
DOI:http://dx.doi.org/10.1371/journal.pone.0006986
ISSN:1932-6203
Parent Title (English):PLoS ONE
Parent Title (English):PLoS one
Publisher:PLoS
Place of publication:Lawrence, Kan.
Document Type:Article
Language:English
Date of Publication (online):2011/09/09
Year of first Publication:2009
Publishing Institution:Univ.-Bibliothek Frankfurt am Main
Release Date:2011/09/09
Volume:4
Issue:9 (e6986)
Pagenumber:11
First Page:1
Last Page:11
Note:
Copyright: © 2009 Martin-Subero et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Source:PLoS ONE 4(9): e6986. doi:10.1371/journal.pone.0006986
HeBIS PPN:276767128
Institutes:Medizin
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Sondersammelgebiets-Volltexte
Licence (German):License LogoCreative Commons - Namensnennung 3.0

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