Comparative analysis of the GNAQ, GNA11, SF3B1, and EIF1AX driver mutations in melanoma and across the cancer spectrum

Uveal melanoma is characterized by recurrent mutations in GNAQ, GNA11, SF3B1, and EIF1AX, as well as a low total mutational burden. The frequency and clinical significance of these mutations in non-uveal melanoma and other cancers is not well described. We identified that GNAQ/GNA11 mutations occur in 0.5–1% of non-uveal melanomas and are essentially melanoma-specific. Further, these mutations are associated with a lack of other typical melanoma mutations (BRAF, NRAS, KIT, NF1), a low mutational burden, and, in a small subset, lack of response to immunotherapy. We suggest that GNAQ/GNA11 mutations characterize an uncommon but distinct subtype of non-uveal melanomas.