Table 2.

Uveal melanoma driver genes and their prognostic significance

Gene	Gene function	Mutation frequency (%)	Association with metastases	Association with survival
GNAQ	Mediating signalling between G‐protein‐coupled receptors and downstream effectors and upregulated MAPK pathway	43–57	Similar frequencies reported between metastatic and non‐metastatic lesions	Mutations have not been linked to patient outcome 113
GNA11	Mediating signalling between G‐protein‐coupled receptors and downstream effectors and upregulated MAPK pathway	41–49	Present in 18/30 (60%) of UM metastases	Disease‐specific survival in GNA11‐mutant patients was 60 months, overall survival 50.6 months (from date of primary tumour), significantly poorer than those tumours lacking GNA11 mutations 117
BAP1	Involved in tumour suppression, DNA damage response and proliferation	70–83	Inactivating somatic mutations in 26/31 (84%) of metastasising tumours. Also associated with Class 2 GEP, M3 and 8q gain.	Overall survival in BAP1 positive nuclear staining by IHC was 9.97 months (95% confidence interval 8.05–11.9) versus BAP1 negative by IHC 4.74 (3.49–6.0) 49, 118, 119
EIF1AX	Eukaryotic translation initiation factor	8–21	Mutant cases are associated with very low risk of metastases (only 2/28 cases)	EIF1AX mutant cases had a longer disease‐free survival than EIF1AX non‐mutant cases (190.1 vs. 100.2 months; p < 0.001) 113, 120, 121
SF3B1	Required for pre‐mRNA splicing	10–24	Intermediate risk of metastases – late‐onset (>5 years) metastases can occur	Although an association of mutated SF3B1 with favourable prognosis was observed in the first few years 122, with longer follow up time, SF3B1 mutant patients developed more metastases and tumours with D3 and SF3B1 mutation showed a significant worse prognosis compared to wild‐type tumours 121, 123