Oncogenic GNAQ and GNA11 Drive Tumorigenesis and Hyper-Pigmentation in a Zebrafish Model of Human Uveal Melanoma

Uveal melanoma is the most common intraocular cancer, with an estimated 2000 cases diagnosed yearly in the U.S. Tumors arise from melanocytes in the choroid, iris, and ciliary body. Treatment typically includes proton beam therapy, and as such, the availability of tissue samples for research is limited. Approximately 50% of patients diagnosed with the disease develop untreatable liver metastases within 15 years. There is an urgent need to develop an animal model for uveal melanoma, in order to discover new therapeutics and understand disease initiation and progression. Approximately 83% of human uveal melanoma tumors have activating mutations in GNAQ or GNA11. Signaling pathways known to cause cell proliferation and survival are active downstream of mutated GNAQ or GNA11, but the exact signals responsible for metastasis remain to be discovered. We have developed a zebrafish model for human uveal melanoma by expressing mutated human GNA11Q209L or GNAQQ209L under control of the zebrafish melanocyte-restrict...