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

Abstract

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 Gαs), and that oncogenic activating mutations in genes encoding Gαq family members (GNAQ or GNA11) are present in ~66% and ~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.

• Authors: Morgan O'Hayre, José Vázquez-Prado, Irina Kufareva, Eric W Stawiski, Tracy M Handel, Somasekar Seshagiri, J Silvio Gutkind
• Journal: Nature reviews. Cancer (Nat Rev Cancer) Vol. 13 Issue 6 Pg. 412-24 (06 2013) ISSN: 1474-1768 [Electronic] England
• PMID: 23640210 (Publication Type: Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Receptors, G-Protein-Coupled
• Heterotrimeric GTP-Binding Proteins

Topics

• Animals
• Gene Expression
• Gene Frequency
• Heterotrimeric GTP-Binding Proteins (genetics, metabolism)
• Humans
• Mutation
• Neoplasms (genetics, metabolism)
• Receptors, G-Protein-Coupled (genetics, metabolism)
• Signal Transduction