EZH2-driven lung cancer as a molecularly distinct entity. EZH2-driven lung cancer as a molecularly distinct entity. A, heatmap of log2 fold-change (LFC) gene expression in murine EZH2-overexpressing (OE) normal lungs (green), KRAS-mutant lung tumors (black), EGFR-mutant lung tumors (blue), and EZH2-OE lung tumors (red). All genes were selected across all samples for clustering. B, box plot of ssGSEA comparing the enrichment of MEK (left) and mTOR (right) gene sets in human TCGA lung adenocarcinomas with specific driver mutations (KRAS, EGFR, unknown) or high EZH2 levels. C, waterfall plot showing rank-ordered change in H3K27ac signal at SE-containing regions between mouse WT lung and EZH2_OE (left), and KRAS and EZH2_OE (right). The x-axis depicts the LFC in H3K27ac signal. SEs are ranked by LFC in signal with regions gaining the most H3K27ac in tumor at the top. D, core transcriptional regulatory circuitry in murine WT and tumor lung tissues (EZH2- or KRAS-driven) as defined by ChIP-seq for H3K27ac. Nodes are transcription factors (TF) that are associated with an SE. Edges indicate a regulatory interaction between two TFs as defined by an enrichment of TF binding motifs in the respective SE. Haikuo Zhang et al. Cancer Discov 2016;6:1006-1021 ©2016 by American Association for Cancer Research