ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2017
Activating cysteinyl leukotriene receptor 2 (CYSLTR2) mutations in blue nevi.
Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 70 citations in OpenAlex.
- Molecular pathology in the diagnosis of cutaneous melanoma.Pathologie (Heidelberg, Germany) · 2026Review
- Cutaneous Melanoma in the Context of Aging.Medicina (Kaunas, Lithuania) · 2025Review
- The role of signaling pathways mediated by the GPCRs CysLTR1/2 in melanocyte proliferation and senescence.Science signaling · 2024Review
- Systems modeling of oncogenic G-protein and GPCR signaling reveals unexpected differences in downstream pathway activation.NPJ systems biology and applications · 2024Article
- Heterogeneity and molecular landscape of melanoma: implications for targeted therapy.Molecular biomedicine · 2024Review
- Diagnosing Cutaneous Melanocytic Tumors in the Molecular Era: Updates and Review of Literature.Dermatopathology (Basel, Switzerland) · 2024Review
- Genetics and RNA Regulation of Uveal Melanoma.Cancers · 2023Review
- Montelukast and Acute Coronary Syndrome: The Endowed Drug.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Review
- Melanoma pathology: new approaches and classification.The British journal of dermatology · 2021Review
- Expanding Our Understanding of Nevogenesis: Copy Number Gain of Chromosome 15q in Melanocytic Nevi Is Associated With Distinct Histomorphologic Findings.The American journal of surgical pathology · 2021Article
- Combined Inhibition of GαClinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Structure-Based Virtual Screening of Ultra-Large Library Yields Potent Antagonists for a Lipid GPCR.Biomolecules · 2020Article
- Article
- Heterotrimeric GThe Journal of biological chemistry · 2020Review
- Uveal melanoma: progress in molecular biology and therapeutics.Therapeutic advances in medical oncology · 2020Review
- New and evolving concepts of melanocytic nevi and melanocytomas.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2020Review
- Structural basis of ligand selectivity and disease mutations in cysteinyl leukotriene receptors.Nature communications · 2019Article
- Harnessing Ion-Binding Sites for GPCR Pharmacology.Pharmacological reviews · 2019Review
- Molecular Characteristics of Uveal Melanoma: Insights from the Cancer Genome Atlas (TCGA) Project.Cancers · 2019Review
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Authors and funding
18 authors at 6 institutions in 4 countries.
Funding
Abstract
Blue nevi are common melanocytic tumors arising in the dermal layer of the skin. Similar to uveal melanomas, blue nevi frequently harbor GNAQ and GNA11 mutations. Recently, recurrent CYSLTR2 and PLCB4 mutations were identified in uveal melanomas not harboring GNAQ or GNA11 mutations. All four genes (GNAQ, GNA11, CYSLTR2, and PLCB4) code for proteins involved in the same signaling pathway, which is activated by mutations in these genes. Given the related functional consequences of these mutations and the known genetic similarities between uveal melanoma and blue nevi, we analyzed a cohort of blue nevi to investigate whether CYSLTR2 and PLCB4 mutations occur in tumors lacking GNAQ or GNA11 mutations (as in uveal melanoma). A targeted next-generation sequencing assay covering known activating mutations in GNAQ, GNA11, CYSLTR2, PLCB4, KIT, NRAS, and BRAF was applied to 103 blue nevi. As previously reported, most blue nevi were found to harbor activating mutations in GNAQ (59%, n=61), followed by less frequent mutations in GNA11 (16%, n=17). Additionally, one BRAF (1%) and three NRAS (3%) mutations were detected. In three tumors (3%) harboring none of the aforementioned gene alterations, CYSLTR2 mutations were identified. All three CYSLTR2 mutations were the same c.386T>A, L129Q mutation previously identified in uveal melanoma that has been shown to lead to increased receptor activation and signaling. In summary, our study identifies CYSLTR2 L129Q alterations as a previously unrecognized activating mutation in blue nevi, occuring in a mutually exclusive fashion with known GNAQ and GNA11 mutations. Similar to GNAQ and GNA11 mutations, CYSLTR2 mutations, when present, are likely defining pathogenetic events in blue nevi.
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