| Gene information | Literature | Expression | lncRNA | Mutation | Homolog |
Basic Information | |
|---|---|
Gene ID | 2776 |
Name | GNAQ |
Synonymous | guanine nucleotide binding protein (G protein), q polypeptide;GNAQ;guanine nucleotide binding protein (G protein), q polypeptide |
Definition | guanine nucleotide-binding protein G(q) subunit alpha|guanine nucleotide-binding protein alpha-q |
Position | 9q21 |
Gene type | protein-coding |
Title | Abstract |
| Oncogenic mutations in GNAQ occur early in uveal melanoma. | PURPOSE: Early/initiating oncogenic mutations have been identified for many cancers, but such mutations remain unidentified in uveal melanoma (UM). An extensive search for such mutations was undertaken, focusing on the RAF/MEK/ERK pathway, which is often the target of initiating mutations in other types of cancer. METHODS: DNA samples from primary UMs were analyzed for mutations in 24 potential oncogenes that affect the RAF/MEK/ERK pathway. For GNAQ, a stimulatory alpha(q) G-protein subunit which was recently found to be mutated in UMs, resequencing was expanded to include 67 primary UMs and 22 peripheral blood samples. GNAQ status was analyzed for association with clinical, pathologic, chromosomal, immunohistochemical, and transcriptional features. RESULTS: Activating mutations at codon 209 were identified in GNAQ in 33 (49%) of 67 primary UMs, including 2 (22%) of 9 iris melanomas and 31 (54%) of 58 posterior UMs. No mutations were found in the other 23 potential oncogenes. GNAQ mutations were not found in normal blood DNA samples. Consistent with GNAQ mutation being an early or initiating event, this mutation was not associated with any clinical, pathologic, or molecular features associated with late tumor progression. CONCLUSIONS: GNAQ mutations occur in about half of UMs, representing the most common known oncogenic mutation in this cancer. The presence of this mutation in tumors at ALL stages of malignant progression suggests that it is an early event in UM. mutations in this G-protein-coupled receptor provide new insights into UM pathogenesis and could lead to new therapeutic possibilities. |
| Hippo-independent activation of YAP by the GNAQ uveal melanoma oncogene through a trio-regulated rho GTPase signaling circuitry. | Mutually exclusive activating mutations in the GNAQ and GNA11 oncogenes, encoding heterotrimeric Galphaq family members, have been identified in approximately 83% and approximately 6% of uveal and skin melanomas, respectively. However, the molecular events underlying these GNAQ-driven malignancies are not yet defined, thus limiting the ability to develop cancer-targeted therapies. Here, we focused on the transcriptional coactivator YAP, a critical component of the Hippo signaling pathway that controls organ size. We found that Galphaq stimulates YAP through a Trio-Rho/Rac signaling circuitry promoting actin polymerization, independently of phospholipase Cbeta and the canonical Hippo pathway. Furthermore, we show that Galphaq promotes the YAP-dependent growth of uveal melanoma cells, thereby identifying YAP as a suitable therapeutic target in uveal melanoma, a GNAQ/GNA11-initiated human malignancy. |