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Array‐based DNA methylation profiling in acute myeloid leukaemia
Author(s) -
Wilop Stefan,
Fernandez Agustín F.,
Jost Edgar,
Herman James G.,
Brümmendorf Tim H.,
Esteller Manel,
Galm Oliver
Publication year - 2011
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2011.08801.x
Subject(s) - myeloid leukaemia , dna methylation , dna profiling , profiling (computer programming) , methylation , dna , computational biology , medicine , biology , cancer research , genetics , gene , computer science , gene expression , operating system
Summary 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.