Comparative pan-cancer DNA methylation analysis reveals cancer common and specific patterns

Abnormal DNA methylation is an important epigenetic regulator involving tumorigenesis. Deciphering cancer common and specific DNA methylation patterns is essential for us to understand the mechanisms of tumor development. The Cancer Genome Atlas (TCGA) project provides a large number of samples of different cancers that enable a pan-cancer study of DNA methylation possible. Here we investigate cancer common and specific DNA methylation patterns among 5480 DNA methylation profiles of 15 cancer types from TCGA. We first define differentially methylated CpG sites (DMCs) in each cancer and then identify 5450 hyper- and 4433 hypomethylated pan-cancer DMCs (PDMCs). Intriguingly, three adjacent hypermethylated PDMC constitute an enhancer region, which potentially regulates two tumor suppressor genes BVES and PRDM1 negatively. Moreover, we identify six distinct motif clusters, which are enriched in hyper- or hypomethylated PDMCs and are associated with several well-known cancer hallmarks. We also observe that PDMCs relate to distinct transcriptional groups. Additionally, 55 hypermethylated and 7 hypomethylated PDMCs are significantly associated with patient survival. Lastly, we find that cancer-specific DMCs are enriched in known cancer genes and cell-type-specific super-enhancers. In summary, this study provides a comprehensive investigation and reveals meaningful cancer common and specific DNA methylation patterns.