title: Array-based DNA methylation profiling in acute myeloid leukaemia.
abstract: Methylation in the promoter region of many genes is involved in regulating gene expression patterns. Using the Illumina GoldenGate© methylation assay, we examined the methylation status of 1505 CpG-sites from 807 genes in 32 samples from patients with acute myeloid leukaemia (AML) at diagnosis, nine at relapse and 15 normal controls and performed additional pyrosequencing and semiquantitative methylation specific polymerase chain reaction (MSP) of the GNMT promoter in 113 diagnostic AML samples. We found a gain of overall methylation in AML samples with a further increase at relapse. Regional hypermethylation as assessed by array analysis could be confirmed by both MSP and pyrosequencing. Additionally, large-scale methylation analysis identified interesting candidate genes. Cluster analysis indicated that cytogenetic subgroups seemed to be characterized by additional distinct epigenetic modifications and that basic DNA methylation patterns remain at relapse. Therefore, promoter hypermethylation is a frequent event in AML and is accentuated at relapse. Array-based methylation analysis determined distinct methylation profiles for non-malignant controls and AML samples with specific chromosomal aberrations and can identify target genes for further evaluation.
authors.affiliation: Medizinische Klinik IV, Universitaetsklinikum Aachen, RWTH Aachen, Pauwelsstrasse 30, Aachen, Germany. swilop@ukaachen.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Wilop
authors.forename: Agustín F
authors.initials: AF
authors.lastname: Fernandez
authors.forename: Edgar
authors.initials: E
authors.lastname: Jost
authors.forename: James G
authors.initials: JG
authors.lastname: Herman
authors.forename: Tim H
authors.initials: TH
authors.lastname: Brümmendorf
authors.forename: Manel
authors.initials: M
authors.lastname: Esteller
authors.forename: Oliver
authors.initials: O
authors.lastname: Galm
mesh_terms: D016022:Case-Control Studies; D002869:Chromosome Aberrations; D016000:Cluster Analysis; D018899:CpG Islands / Q000235:genetics; D016172:DNA Fingerprinting / Q000379:methods; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D050938:Glycine N-Methyltransferase / Q000235:genetics; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D012008:Recurrence
chemical_list: D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; C494510:GNMT protein, human; D050938:Glycine N-Methyltransferase