title: GNAQ and GNA11 mutations in uveal melanoma.
abstract: G-protein-coupled receptors signal through heterotrimeric G proteins, Gα and G-βγ, to manage numerous aspects of physiologic homeostasis. Many neoplastic processes harbor alterations in G-protein-coupled receptors and/or G-α proteins, best exemplified by recurrent activating mutations in GNAQ or GNA11 in uveal melanomas. This review will discuss the multiple activated signaling targets downstream of mutant GNAQ and GNA11 in uveal melanoma, including MEK, PI3-kinase/Akt, protein kinase C, and YAP. This knowledge has led to the rapid expansion of clinical trials that are specific to patients with uveal melanoma and promises future breakthroughs in therapies.
authors.affiliation: aMelanoma and Immunotherapeutics Service bDepartment of Developmental Therapeutics, Melanoma and Immunotherapeutics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Shoushtari
authors.forename: Richard D
authors.initials: RD
authors.lastname: Carvajal
mesh_terms: D000818:Animals; D002864:Chromogranins; D044385:GTP-Binding Protein alpha Subunits / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics; D006801:Humans; D008545:Melanoma / Q000235:genetics*; D009154:Mutation; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics; D014604:Uveal Neoplasms / Q000235:genetics*; D000098943:Uveal Melanoma
chemical_list: D002864:Chromogranins; C554062:GNA11 protein, human; C554061:GNAQ protein, human; D044385:GTP-Binding Protein alpha Subunits; D043562:Receptors, G-Protein-Coupled; C406732:GNAS protein, human; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D019205:GTP-Binding Protein alpha Subunits, Gs