Stains & molecular markers

Topic Completed: 1 April 2014

Minor changes: 8 December 2020

Copyright: 2003-2021,, Inc.

PubMed Search: GNAQ[TI]

Liang Cheng, M.D.
Page views in 2020: 62
Page views in 2021 to date: 7
Cite this page: Bradish, J., Cheng L. GNAQ. website. Accessed January 17th, 2021.
Definition / general
  • G proteins encode guanine nucleotide binding proteins, a group of heterotrimeric proteins (composed of α, β and γ subunits) involved in intracellular cascades (Science 2002;296:1636, Nature 2009;459:356)
  • GNAQ specifically encodes the alpha subunit, which binds GTP for activation and is hydrolyzed to GDP for inactivation
  • Hydrolysis is intrinsically mediated by the alpha subunit
  • Binding of GTP causes disassociation of the alpha subunit from the beta subunit
  • Both alpha and beta subunits are able to propagate cellular signaling pathways (Mol Cell Biol 1992;12:4687)
Diagrams / tables

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Frequency of GNAQ mutations

Clinical features
  • GNAQ mutations:
    • Found frequently in uveal melanoma (46%), malignant blue nevus (50%) and blue nevus (83%) (Nature 2009;457:599); very rare in other types of melanoma
    • Mostly mutually exclusive with other mutations (BRAF, KIT, etc.)
    • Alone are insufficient for full progression to melanoma; appears to be an early mutation in its development (Nature 2009;457:599)
    • Do not correlate with disease free survival in uveal melanoma (Br J Cancer 2009;101:813)
  • Although not currently available, GNAQ is an attractive target for inhibitor development:
    • Preclinical data suggests that a melanoma cell line harboring the GNAQ Q209L is sensitive to MEK inhibition
    • A few ongoing phase I and phase II clinical trials may help elucidate the effectiveness of various therapies in patients with metastatic melanoma of the eye (My Cancer Genome: GNAQ in Melanoma [Accessed 12 June 2018])
Mechanisms of resistance
  • None yet described
Resistance therapies
  • None yet evaluated
Molecular / cytogenetics description
  • GNAQ mutations appear to mainly occur in codon 209, a RAS-like domain necessary for GTPase activity
  • This mutation results in constitutive activation of the GNAQ protein, which causes it to behave as a dominant acting oncogene (Nature 2009;457:599)
  • GNAQ mutations in exon 5, at codon 209 are most common and include Q209P > Q209L > Q209R (Br J Cancer 2009;101:813)
  • Less common mutations in exon 4, at codon 183 have also been described (N Engl J Med 2010;363:2191)
  • Specific mutations are detected using PCR based DNA Sanger sequencing
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