title: A comprehensive microarray-based DNA methylation study of 367 hematological neoplasms.
abstract: 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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Institute of Human Genetics, Christian-Albrechts University, Kiel, Germany. jimartin@idibell.cat
authors.forename: Jose I
authors.initials: JI
authors.lastname: Martin-Subero
authors.forename: Ole
authors.initials: O
authors.lastname: Ammerpohl
authors.forename: Marina
authors.initials: M
authors.lastname: Bibikova
authors.forename: Eliza
authors.initials: E
authors.lastname: Wickham-Garcia
authors.forename: Xabier
authors.initials: X
authors.lastname: Agirre
authors.forename: Sara
authors.initials: S
authors.lastname: Alvarez
authors.forename: Monika
authors.initials: M
authors.lastname: Brüggemann
authors.forename: Stefanie
authors.initials: S
authors.lastname: Bug
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Calasanz
authors.forename: Martina
authors.initials: M
authors.lastname: Deckert
authors.forename: Martin
authors.initials: M
authors.lastname: Dreyling
authors.forename: Ming Q
authors.initials: MQ
authors.lastname: Du
authors.forename: Jan
authors.initials: J
authors.lastname: Dürig
authors.forename: Martin J S
authors.initials: MJ
authors.lastname: Dyer
authors.forename: Jian-Bing
authors.initials: JB
authors.lastname: Fan
authors.forename: Stefan
authors.initials: S
authors.lastname: Gesk
authors.forename: Martin-Leo
authors.initials: ML
authors.lastname: Hansmann
authors.forename: Lana
authors.initials: L
authors.lastname: Harder
authors.forename: Sylvia
authors.initials: S
authors.lastname: Hartmann
authors.forename: Wolfram
authors.initials: W
authors.lastname: Klapper
authors.forename: Ralf
authors.initials: R
authors.lastname: Küppers
authors.forename: Manuel
authors.initials: M
authors.lastname: Montesinos-Rongen
authors.forename: Inga
authors.initials: I
authors.lastname: Nagel
authors.forename: Christiane
authors.initials: C
authors.lastname: Pott
authors.forename: Julia
authors.initials: J
authors.lastname: Richter
authors.forename: José
authors.initials: J
authors.lastname: Román-Gómez
authors.forename: Marc
authors.initials: M
authors.lastname: Seifert
authors.forename: Harald
authors.initials: H
authors.lastname: Stein
authors.forename: Javier
authors.initials: J
authors.lastname: Suela
authors.forename: Lorenz
authors.initials: L
authors.lastname: Trümper
authors.forename: Inga
authors.initials: I
authors.lastname: Vater
authors.forename: Felipe
authors.initials: F
authors.lastname: Prosper
authors.forename: Claudia
authors.initials: C
authors.lastname: Haferlach
authors.forename: Juan
authors.initials: J
authors.lastname: Cruz Cigudosa
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism; D016000:Cluster Analysis; D018899:CpG Islands; D019175:DNA Methylation; D020869:Gene Expression Profiling; D019337:Hematologic Neoplasms / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D011401:Promoter Regions, Genetic; D013601:T-Lymphocytes / Q000378:metabolism