DNA hypermethylation encroachment at CpG island borders in cancer is predisposed by H3K4 monomethylation [WGBS_Hs]

DNA methylation plays a key role in demarcation of regulatory regions, including promoter-associated CpG islands. While CpG islands are typically maintained in an unmethylated state in normal cells, a proportion of CpG islands are subject to hypermethylation in cancer cells. It still remains elusive how the exquisite demarcation of the bimodal methylation state is established and maintained at the CpG island flanks and conversely what triggers the erosion of CpG island DNA methylation in tumorigenesis. Here, we applied whole-genome bisulphite sequencing to study the comprehensive methylation patterns of prostate normal and cancer tissues. Alongside we performed TET-assisted bisulphite sequencing to study genome-wide DNA hydroxymethylation patterns of normal prostate and prostate cancer tissues. Clinical prostate samples were identified from the Garvan Institute/St Vincent's Prostate Cancer biobank with human ethics approval (SVH File Number 12/231). Formalin-fixed, paraffin-embedded radical prostatectomy blocks were retrieved and H&E sections reviewed by a specialist prostate cancer pathologist. Five 2 mm core biopsies were taken from 1) each of the dominant nodules in areas of >90% cancer cell density, and 2) adjacent benign prostate tissue. DNA was extracted using the AllPrep DNA/RNA kit (Qiagen, USA).