Characteristics Of DNA Methylation In Cancers And Reclassifications Of Cancer Subtypes Based On DNA Methylome Profiles

DNA methylation is one of the most important epigenetic phenomena.The disturbances of DNA methylation in cancers are ubiquitous and they are connected with tumorigenesis frequently.However,there are more than one explainations about their relationships.Recent studies found that different cancer types contained distinct patterns of DNA methylation.DNA methylome profiles were used in the field of cancer subtype research,while integrative analyses across multiple cancer types remained limited.In this research,we collected DNA methylome profiles and gene expression profiles of 7,055 tumorous samples and about 600 parallel normal tissue samples in 21 cancer types from TCGA.We investigated characteristics of DNA methylation in cancers in a pan-cancer manner.We then analyzed potential relationships between methylation levels in CpG sites of promoter regions and expression levels of their corresponding genes.Finally,based on methylome profiles from CpG sites with the most highly heterogeneous methylation across all tumorous samples,we performed a hierarchical clustering analysis to study the convergence of tumorous patients.We found that the disturbed expression levels of transcription factors in cancers were partly due to the disturbed methylation levels in promoter regions.We found that the relationship between DNA methylation and gene expression was bi-directional,because it not only could be a negative correlation but also could be a positive correlation.Thought patterns of DNA methylation in promoter regions were cancer-specific,patients from different cancer types could be gathered into a same subcluster,and patients from the same cancer type could be separated into multiple subclusters.Further more,subclusters from hierarchical clustering analysis showed significant differences in survival analyses.In short,we performed experiments with a pan-cancer manner on DNA methylome profiles across multiple cancer types,investigating characteristics of DNA methylation in cancers and reclassifing cancer subtypes.We had generated a series of resources for further investigations.