ArticleInvestigative ophthalmology & visual science2019
Heterogeneity in Mitogen-Activated Protein Kinase (MAPK) Pathway Activation in Uveal Melanoma With Somatic GNAQ and GNA11 Mutations.
Article in Investigative ophthalmology & visual science, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Uveal Melanocytoma without GNAQ/GNA11 Mutations.Ocular oncology and pathology · 2025Article
- Neuropeptide Precursor VGF Promotes Liver Metastatic Colonization of Gαq Mutant Uveal Melanoma by Facilitating Tumor Microenvironment via Paracrine Loops.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- GNAQ/GNA11-Related Benign and Malignant Entities-A Common Histoembriologic Origin or a Tissue-Dependent Coincidence.Cancers · 2024Review
- Article
- MEK inhibition reduced vascular tumor growth and coagulopathy in a mouse model with hyperactive GNAQ.Nature communications · 2023Article
- PTK6 inhibits autophagy to promote uveal melanoma tumorigenesis by binding to SOCS3 and regulating mTOR phosphorylation.Cell death & disease · 2023Article
- Investigating the Role of DUSP4 in Uveal Melanoma.Translational vision science & technology · 2022Article
- Review
- MITF deficiency accelerates GNAQ-driven uveal melanoma.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Uveal Melanoma Cell Line Proliferation Is Inhibited by Ricolinostat, a Histone Deacetylase Inhibitor.Cancers · 2022Article
- GNAQ mutations drive port wine birthmark-associated Sturge-Weber syndrome: A review of pathobiology, therapies, and current models.Frontiers in human neuroscience · 2022Review
- mMolecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Melanoma Plasticity: Promoter of Metastasis and Resistance to Therapy.Frontiers in oncology · 2021Review
- Update onCancers · 2020Review
- Clinicopathological and prognostic significance and molecular mechanisms governing uveal melanoma.Therapeutic advances in medical oncology · 2020Review
- Secondary Somatic Mutations in G-Protein-Related Pathways and Mutation Signatures in Uveal Melanoma.Cancers · 2019Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Purpose: The activation of the mitogen-activated protein kinase (MAPK) pathway has been suggested as the major downstream target when GNAQ and GNA11 (GNAQ/11) are mutated in uveal melanoma (UM). However, clinical trials with single agent MEK inhibitor showed no clinical significance in altering the overall outcome of the disease in UM; therefore, we investigated the correlation between naturally occurring mutations in GNAQ/11 and activation of MAPK pathway in vivo in primary UM. Methods: Screening for activating mutations in codons 183 and 209 of GNAQ/11 was carried out by sequencing and restriction fragment length polymorphism (RFLP) in a cohort of 42 primary UM. Activation of the MAPK pathway and other potential downstream signals was assessed by immunohistochemistry and/or Western blot analysis. Potential downstream signaling of mutant and wild type GNAQ/11 was studied by transient transfection assay in nonmutant cell lines. Results: Somatic mutations in GNAQ/11 were observed in 35/42 (83.3%) of primary UM. Tumors with GNAQ/11 mutations showed variations in the activation of ERK1/2 with significant tumor heterogeneity. Weak and undetectable ERK1/2 activation was observed in 4/35 (11.4%) and 8/35 (22.9%) of the GNAQ/11 mutant UM, respectively. Tumor heterogeneity of GNAQ/11 mutations was also observed in a subset of tumors. Conclusions: Our results indicate that there is marked variation in MAPK activation in UM with GNAQ/11 mutations. Thus, GNAQ/11 mutational status is not a sufficient biomarker to adequately predict UM patient responses to single-agent selective MEK inhibitor therapy.
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