Frequent somatic mutations of GNAQ in uveal melanoma and blue nevi

By Catherine D. Van Raamsdonk, V. Bezrookove, G. Green, J. Bauer, Lona Gaugler, J. O'Brien, E. M. Simpson, G. Barsh, Boris C. Bastian. Nature, 2008

1,381 citations recorded by the source corpus.

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.

Subfields: Immunology and Allergy, Molecular Biology, Ophthalmology

View Paper: https://www.semanticscholar.org/paper/4826acb081f5d0dcd3b6651bd75e9714f1793912

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

1. Gad Getz
2. Eric S. Lander
3. Fa-Xing Yu
4. Matthew Meyerson
5. Katherine A. Hoadley
6. K. Guan
7. D. Hayes
8. Yiling Lu

Citations in the corpus

• Integrative Analysis Identifies Four Molecular and Clinical Subsets in Uveal Melanoma. (2018, result): “and Clinical Subsets in Uveal Melanoma A. Gordon Robertson,1,35 Juliann Shih,2,3,35 Christina Yau,4,35 Ewan A. Gibb,1 Junna Oba,5 Karen L. Mungall,1 Julian M. Hess,2 Vladislav Uzunangelov,6 Vonn Walter,7,8 Ludmila Danilova,9 Tara M. Lichtenberg,10 Melanie Kucherlapati,11,12 Patrick K. Kimes,7 Ming T”
• The Hippo pathway: regulators and regulations. (2013, background): “Activating mutations of Ga are also present in different types of cancers: Gaq/11-activating mutations have been identified in >80% of uveal melanomas (Van Raamsdonk et al. 2009, 2010); Gai2a and Gas mutations have been identified in ovarian and endocrine tumors (Lania et al. 2001).”