DNA co-methylation networks outline the structure and remodeling dynamics of colorectal cancer epigenome

Epigenomic plasticity is interconnected with chromatin structure and gene regulation. In tumor progression, orchestrated remodeling of genome organization accompanies the acquisition of malignant properties. DNA methylation, a key epigenetic mark extensively altered in cancer, is also linked to genome architecture and function. Based on this association, we postulate that the dissection of long-range co-methylation structure unveils cancer cells genome architecture remodeling. We applied network-modeling of DNA methylation co-variation in two colon cancer cohorts and found abundant and consistent transchromosomal structures in both normal and tumor tissue. Normal-tumor comparison indicated substantial remodeling of the epigenome covariation and revealed novel genomic compartments with a unique signature of DNA methylation rank inversion.