BACKGROUND: Perturbation of DNA methylation is frequent in cancers and has 
emerged as an important mechanism involved in tumorigenesis. To determine how 
DNA methylation is modified in the genome of primary glioma, we used Methyl-DNA 
immunoprecipitation (MeDIP) and Nimblegen CpG promoter microarrays to identify 
differentially DNA methylation sequences between primary glioma and normal brain 
tissue samples.
METHODS: MeDIP-chip technology was used to investigate the whole-genome 
differential methylation patterns in glioma and normal brain tissues. 
Subsequently, the promoter methylation status of eight candidate genes was 
validated in 40 glioma samples and 4 cell lines by Sequenom's MassARRAY system. 
Then, the epigenetically regulated expression of these genes and the potential 
mechanisms were examined by chromatin immunoprecipitation and quantitative 
real-time PCR.
RESULTS: A total of 524 hypermethylated and 104 hypomethylated regions were 
identified in glioma. Among them, 216 hypermethylated and 60 hypomethylated 
regions were mapped to the promoters of known genes related to a variety of 
important cellular processes. Eight promoter-hypermethylated genes (ANKDD1A, 
GAD1, HIST1H3E, PCDHA8, PCDHA13, PHOX2B, SIX3, and SST) were confirmed in 
primary glioma and cell lines. Aberrant promoter methylation and changed histone 
modifications were associated with their reduced expression in glioma. In 
addition, we found loss of heterozygosity (LOH) at the miR-185 locus located in 
the 22q11.2 in glioma and induction of miR-185 over-expression reduced global 
DNA methylation and induced the expression of the promoter-hypermethylated genes 
in glioma cells by directly targeting the DNA methyltransferases 1.
CONCLUSION: These comprehensive data may provide new insights into the 
epigenetic pathogenesis of human gliomas.