Impact of recurrent mutations on the transcriptome. (A) Plot displaying sets of genes identified as showing significant cis- or trans-effects on gene expression based on xseq analysis. (B) Oncoplot showing the distribution of mutations in genes with a trans-effect across the entire cohort. Gene association networks for significant trans-influencing genes exemplified by (C) JAK1, (D) RELB, and (E) EP300 based on xseq analysis. Nodes represent genes within the interaction network, and edges are interactions between genes based on the global influence network (see "Methods" for details). Nodes are colored by average log2 normalized expression across patients whose tumors harbor mutations, with red indicating high expression and blue indicating low expression. Genes with green borders in the network are functionally enriched for the JAK-STAT signaling pathway (panel C, FDR, P = 4.44E-72) or the NF-κB signaling pathway (panel D, FDR, P = 8.13E-27), respectively. In panel E, the green and purple borders highlight genes enriched in pathways related to epigenetic regulation, specifically the regulation of transcription (FDR, P = 8.3E-47) and the regulation of nucleic acid–templated transcription (FDR, P = 4.83E-43), respectively.