Increased methylation variation in epigenetic domains across cancer types

摘要: Tumor heterogeneity is a major barrier to effective cancer diagnosis and treatment. We recently identified cancer-specific differentially DNA-methylated regions (cDMRs) in colon cancer, which also distinguish normal tissue types from each other, suggesting that these cDMRs might be generalized across types. Here we show stochastic methylation variation of the same cDMRs, distinguishing tissue, colon, lung, breast, thyroid Wilms' tumors, with intermediate adenomas. Whole-genome bisulfite sequencing shows variable are related loss sharply delimited boundaries at CpG islands. Furthermore, find hypomethylation discrete blocks encompassing half genome, extreme gene expression variability. Genes associated large involved mitosis matrix remodeling, respectively. suggest model for involving epigenetic stability well-defined genomic domains underlies increased variability may contribute tumor heterogeneity.