Fig. 1

Identifying cancer-specific DNA methylation changes in distal enhancer regions. a Out of 145,265 distal probes on the HM450k platform, 102,518 were contained within our annotated enhancer regions (with approximately 1/8 of all distal enhancers being covered by at least one probe). b The statistical method used to identify probes hypomethylated (or hypermethylated) in cancer (see Methods for additional details). The heatmap in the top panel shows the DNA methylation level at each probe p_i for each sample from a particular cancer type (either an adjacent normal, or a tumor). Each cell is a methylation β value, reflecting the fraction of methylated DNA molecules at each CpG probe. The remainder of the panel illustrates our statistical test, which compares only the most extreme 20 % of normal samples to the most extreme 20 % of tumor samples, in order to identify probes hypomethylated in only a subset of tumors. (c) Shown is a histogram representing the number of cancer-specific hypomethylated (top graph) or hypermethylated (bottom graph) distal enhancer probes identified for each cancer type. The fraction of these probes shared by one or more other tumor types is indicated by the color bars (1 indicates that the probe is hypomethylated in only that tumor type, 2 indicates that it is hypomethylated in one other tumor type, and so on)