Analysis of promoter non-CG methylation in prostate cancer

In vertebrates, DNA methylation occurs primarily at CG dinucleotides but recently, non-CG methylation has been found at appreciable levels in embryonic stem cells.

To assess non-CG methylation in cancer, we compared the extent of non-CG methylation at several biologically important CG islands in prostate cancer and normal cell lines. An assessment of the promoter CG islands EVX1 and FILIP1L demonstrates a fourfold higher rate of non-CG methylation at EVX1 compared with FILIP1L across all cell lines. These loci are densely methylated at CG sites in cancer.

No significant difference in non-CG methylation was demonstrated between cancer and normal. Treatment of cancer cell lines with 5-azacytidine significantly reduced methylation within EVX1 at CG and CC sites, preferentially.

Non-CG methylation does not correlate with CG methylation at hypermethylated promoter regions in cancer. Furthermore, global inhibition of DNA methyltransferases does not affect all methylated cytosines uniformly.