Our findings reveal that the molecular properties of Gα<sub>q</sub> Q209P are fundamentally different from those in other active Gα<sub>q</sub> proteins and could be leveraged as a specific vulnerability for the ∼20% of UMs bearing this mutation.
Sequencing of melanoma driver genes revealed GNAQ (p.Q209L) mutations in two samples; although it is possible that these samples represent extraocular spread of an occult uveal melanoma.
Overall, this model offers a new tool to dissect signaling by oncogenic GNAQ and to test potential therapeutics in an in vivo setting where GNAQ(Q209L) mutations contribute to both the initiation and metastatic progression of uveal melanoma.