Abstract
We profiled 110 fresh frozen tumor samples that cover 11 common solid cancer types using whole-genome bisulfite sequencing at high depth, identifying a total of 81,567 non-redundant MHBs. These cancer MHBs were significantly enriched in regulatory elements defined by ATAC-seq and ChIA-PET in a context-specific manner. Integrative analysis from both bulk and single-cell data demonstrated that these MHBs were also associated with gene expression, likely through a mechanism that is independent of mean methylation. Moreover, MHBs-associated differentially expressed genes in pan-cancer were prioritized for the involvement in core cancer-related pathways such as G2M, MYC and E2F targets. Finally, aging-associated blocks arising from this study were demonstrated to be recurrently hyper-methylated in premalignant lesions of 9 cancer types.
