Fig. 3.

A schematic view of main molecular events in uveal melanoma (UM) progression. The earliest event is an activating mutation in GNAQ or GNA11, probably in a normal uveal melanocyte. This triggers inappropriate cell cycle through activation of the mitogen-activated protein kinase (MAPK) and perhaps other pathways. Usually the mutant cell clone does not progress into melanoma and is eliminated by apoptosis (black spheres). Rarely nevus will transform to low-risk or high-risk UM. Low-risk melanoma (blue sphere) demonstrates low risk for metastasis and often exhibits chromosome 6p gain and EIFA1X gene mutation and carries <10% risk for metastasis (small purple sphere). In contrast, melanomas classified as high risk (red sphere) often show chromosome 3 monosomy and mutation in BRCA1-associated protein-1 (BAP1) gene with >50% risk for metastasis (large purple sphere).