Stains & molecular markers
GNAQ
Copyright: 2003-2021, PathologyOutlines.com, Inc.
PubMed Search: GNAQ[TI]
GNAQ
Authors: Joshua R. Bradish, M.D., Liang Cheng, M.D.
Topic Completed: 1 April 2014
Minor changes: 8 December 2020
Copyright: 2003-2021, PathologyOutlines.com, Inc.
PubMed Search: GNAQ[TI]
Table of Contents
Definition / general | Diagrams / tables | Clinical features | Treatment | Mechanisms of resistance | Resistance therapies | Molecular / cytogenetics descriptionCite this page: Bradish, J., Cheng L. GNAQ. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsGNAQ.html. 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
Images hosted on other servers:
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)
Treatment
- 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
