TY  - JOUR
A1  - Martin-Subero, Jose Ignacio
A1  - Ammerpohl, Ole
A1  - Bibikova, Marina
A1  - Wickham-Garcia, Eliza
A1  - Agirre, Xabier
A1  - Alvarez, Sara
A1  - Brüggemann, Monika
A1  - Bug, Stefanie
A1  - Calasanz, Maria J.
A1  - Deckert, Martina
A1  - Dreyling, Martin
A1  - Du, Ming Q.
A1  - Dürig, Jan
A1  - Dyer, Martin J. S.
A1  - Fan, Jian-Bing
A1  - Gesk, Stefan
A1  - Hansmann, Martin-Leo
A1  - Harder, Lana
A1  - Hartmann, Sylvia
A1  - Klapper, Wolfram
A1  - Küppers, Ralf
A1  - Montesinos-Rongen, Manuel
A1  - Nagel, Inga
A1  - Pott, Christiane
A1  - Richter, Julia
A1  - Román-Gómez, José
A1  - Seifert, Marc
A1  - Stein, Harald
A1  - Suela, Javier
A1  - Trümper, Lorenz
A1  - Vater, Inga
A1  - Prosper, Felipe
A1  - Haferlach, Claudia
A1  - Cruz Cigudosa, Juan
A1  - Siebert, Reiner
T1  - A comprehensive microarray-based DNA methylation study of 367 hematological neoplasms
T2  - PLoS One
N2  - 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.
Y1  - 2011
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/22667
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30-115114
SN  - 1932-6203
N1  - 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.
VL  - 4
IS  - (9): e6986
SP  - 1
EP  - 11
PB  - PLoS
CY  - Lawrence, Kan.
ER  -