Modular dynamics of DNA co-methylation networks exposes the functional organization of colon cancer cells' genome

DNA methylation dynamics is intrinsically interconnected with processes underlying the malignant properties of cancer cells. By applying network-based approaches in two series of colorectal cancers we dissected the long-range co-methylation structure finding consistent patterns of compartmentalization in both normal and tumor tissues. Large transchromosomal modules showed unique regulatory signatures and coalesced into a structured network and allowing simple patient stratification. Normal-tumor comparison revealed substantial remodeling of specific modules and migration of subsets of co-methylating sites denoted by functional aggregates, pointing out potential sources of epigenetic and phenotypic variability. We conclude that DNA methylation dynamics architecture embodies interpretable information that can be used as a proxy of the drivers and the phenotypes of malignant transformation.