The emerging mutational landscape of G proteins and G-protein-coupled receptors in cancer

Aberrant expression and activity of G proteins and G-protein-coupled receptors (GPCRs) are frequently associated with tumorigenesis. Deep sequencing studies show that 4.2% of tumours carry activating mutations in GNAS ( encoding G alpha(s)), and that oncogenic activating mutations in genes encoding G alpha(q) family members (GNAQ or GNA11) are present in similar to 66% and similar to 6% of melanomas arising in the eye and skin, respectively. Furthermore, nearly 20% of human tumours harbour mutations in GPCRs. Many human cancer-associated viruses also express constitutively active viral GPCRs. These studies indicate that G proteins, GPCRs and their linked signalling circuitry represent novel therapeutic targets for cancer prevention and treatment.