Abstract
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 cell’s 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.
Competing Interest Statement
MAP is cofounder and equity holder of Aniling, a biotech company with no interests in this paper. MAP lab has received research funding from Celgene. The rest of the authors declare no conflict of interest.
