Identification of markers associated with global changes in DNA methylation regulation in cancers

DNA methylation exhibits different patterns in different cancers. DNA methylation rates at different genomic loci appear to be highly correlated in some samples but not in others. We call such phenomena conditional concordant relationships (CCRs). In this study, we explored DNA methylation patterns in 12 common cancers using data of 2434 patient samples collected by The Cancer Genome Atlas project. We developed an exploratory method to characterize CCRs in the methylation data and identified the 200 gene markers whose on-and-off statuses in DNA methylation are most significantly associated with drastic changes in CCRs throughout the genome. Clustering analysis of the methylation data of the 200 markers showed that they are tightly associated with cancer subtypes. We also generated a library of the significant CCRs that may be of interest to future studies of the regulation network of DNA methylation in cancer.