Fig. 4

Transcription factors expressed in normal tissue and silenced in cancer predominantly exhibit promoter hypermethylation and not genomic loss or inactivating mutation. Left panels: density plots of t-statistics of differential DNAm between cancer and normal tissue (x-axis, t(C − N)) of the tissue-specific cancer-silenced TFs (magenta lines) compared with the corresponding density distribution of all genes underexpressed in cancer (green lines). Density plots are shown for six cancer types: LSCC, LUAD, KIRC, KIRP, BLCA and COAD. P values are from a Wilcoxon rank sum test. The vertical magenta and green lines denote the average levels. The grey vertical lines in the DNAm plot indicate P = 0.05. Middle panels: as above but for the average CNV segment values of the TFs (magenta lines) and all underexpressed genes (green lines). Right panels: as above but for the frequency of inactivating mutation of the TFs (magenta lines) and all underexpressed genes (green lines)