Fig. 4

Gain of function of VHL mutations enhance hypoxia signaling and glycolysis pathways. A, B Volcano plots of differentially expressed genes in 786-O cells expressing VHL mutations, S65P (A) or S65W (B), compared with VHL WT control. Significantly altered genes (adjusted p value < 0.05; fold change >  ± 2) are indicated in green (upregulated) or dark blue (downregulated). Top ranked VHL mutation-influenced genes are selectively labeled. C, D GSEA-determined hypoxia (C) or glycolysis (D) pathways with S65W-influenced gene signature. Genes are ranked by their expression levels in 786-O cells expressing VHL mutation S65W. Plots in the right of C or D show HIF2α ChIP-seq signals of 5 kb around the transcriptional start sites (TSS) of altered genes in hypoxia (C) or glycolysis (D) pathways