Fig. 7. 5′-UTR mutations in MAP kinase signaling pathway genes associated with increased pathway activity and metastases in prostate cancer patients.

a Genes with 5′-UTR mutations in localized and advanced prostate cancer cluster into distinct functional categories as determined by KEGG pathway analysis (Fisher’s hypergeometric test, FDR < 0.05). b Heatmap of a MAP kinase pathway activity signature demonstrating that patients with functional 5′-UTR mutations to MAP kinase regulators (PLUMAGE FDR < 0.1) exhibit increased pathway activation compared to nonfunctional mutations (PLUMAGE FDR > 0.1). The heatmap color key represents normalized log₂(CPM + 1) values for each gene. c Metastatic castration-resistant prostate cancer patients harbor 5′-UTR mutations within genes found in the MAP kinase signaling pathway. Gene names in green represent those with 5′-UTR mutations in mCRPC patients. Gene names in gray are MAP kinase signaling pathway components and downstream effectors that are not mutated in mCRPC patients. d mCRPC patients with mutated MAP kinase pathway genes are significantly more prone to bone metastases at diagnosis (black) compared to patients who do not harbor these mutations (green) (p = 0.045, two-sided Student’s t test). e The difference in bone metastasis at diagnosis between the two patient groups is independent of any differences in 5′-UTR tumor mutational burden (n.s. not statistically significant, two-sided Student’s t test). Source data are provided as a Source data file.