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Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi
Open accessAbstract
BRAF and NRAS are common targets for somatic mutations in benign and malignant neoplasms that arise from melanocytes situated in epithelial structures, and lead to constitutive activation of the mitogen-activated protein (MAP) kinase pathway. However, BRAF and NRAS mutations are absent in a number of other melanocytic neoplasms in which the equivalent oncogenic events are currently unknown. Here we report frequent somatic mutations in the heterotrimeric G protein α-subunit, GNAQ, in blue naevi (83%) and ocular melanoma of the uvea (46%). The mutations occur exclusively in codon 209 in the Ras-like domain and result in constitutive activation, turning GNAQ into a dominant acting oncogene. Our results demonstrate an alternative route to MAP kinase activation in melanocytic neoplasia, providing new opportunities for therapeutic intervention.
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Mutations of the BRAF gene in human cancer
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High frequency of BRAF mutations in nevi
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Hippo pathway in organ size control, tissue homeostasis, and cancer
Yu, F.-X., Zhao, B., & Guan, K.-L. (2015) · Cell · doi:10.1016/j.cell.2015.10.044 · Cited by 2,206
The Hippo pathway: regulators and regulations.
Yu, F.-X., & Guan, K.-L. (2013) · Genes & Development · doi:10.1101/gad.210773.112 · Cited by 1,231
Frequency of TERT promoter mutations in human cancers
Vinagre, J., Almeida, A., Pópulo, H., Batista, R., Lyra, J., Pinto, V., Coelho, R., Celestino, R., Prazeres, H., Lima, L., et al. (2013) · Nature Communications · doi:10.1038/ncomms3185 · Cited by 898
Long, G. V., Swetter, S. M., Menzies, A. M., Gershenwald, J. E., & Scolyer, R. A. (2023) · The Lancet · doi:10.1016/s0140-6736(23)00821-8 · Cited by 746
Hodi, F. S., Corless, C. L., Giobbie-Hurder, A., Fletcher, J. A., Zhu, M., Marino-Enriquez, A., Friedlander, P., Gonzalez, R., Weber, J. S., Gajewski, T. F., et al. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2012.47.7836 · Cited by 608
Metadata
- Authors
- Van Raamsdonk, C. D., Bezrookove, V., Green, G., Bauer, J., Gaugler, L., O’Brien, J. M., Simpson, E. M., Barsh, G. S., & Bastian, B. C.
- Venue
- Nature
- Published
- 2008-12-10
- Volume
- 457
- Issue
- 7229
- Pages
- 599-602
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2053520756
- Cited by
- 1,623
- References
- 4
- FWCI
- 48.04
- Type
- journal article
- Language
- en
- Open access
- green
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- Van Raamsdonk, C. D., Bezrookove, V., Green, G., Bauer, J., Gaugler, L., O’Brien, J. M., Simpson, E. M., Barsh, G. S., & Bastian, B. C. (2009). Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi. Nature. https://doi.org/10.1038/nature07586
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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