Table 1.
Main gene mutations in uveal melanoma.
| Gene Mutation | Gene Function | Dysregulation | Reference |
|---|---|---|---|
| GNAQ/GNA11 | Responsible for extracellular signal transduction and intracellular pathways activation | 91% of UM patients (principal driver of carcinogenesis) GNAQ/GNA11 mutations are mutually exclusive Mutations in GNAQ have a prevalence of 42.2%, whereas in GNA11 is 32.6%. GNAQ/GNA11 mutations activate MEK and the oncoprotein YAP |
[31,32,33,34,35,36,37,38] |
| CYSLTR2 | Involved in leukotriene-mediated signalling in inflammation and fibrosis | Leu129Gln substitution founded only in samples lacking mutations in GNAQ, GNA11, and PLCB4 activation of Gαq signalling |
[39,40] |
| PLCB4 | Roles in the metabolism of inositol lipids and cancer | PLCB4 p.D630Y mutations are mutually exclusive with mutations in GNA11 and GNAQ | [41] |
| BAP1 | Nuclear ubiquitin carboxyl-terminal hydrolase enzyme with deubiquitinase activity | 22% in familial UM (associated with early UM onset) BAP1 mutations cause loss of protein expression and loss of function and cell phenotype modifications BAP1 depletion increases the amount of transmigration in UM cells |
[23,39,40,41,42,43,44,45,46,47,48,49] |
| SF3B1 | Involved in mRNA splicing | Detected in 15%–19% of UM cases Mutation at codon 625 of SF3B1 gene is associated with UM development. Cause splicing dysregulations and alter the transcription process Mutually exclusive to BAP1 mutations Associated with the chromosome 3 disomy Associated with good prognosis and low metastatic potential |
[54,55,56,57] |
| EIF1AX | Stimulates the transfer of Met-tRNAi to the ribosomal subunit | Detected in 8%–18.9% of primary UM cases. Alterations in EIF1AX gene are usually missense mutations It was suggested that an abnormal translation process might be responsible for a clonal selective advantage in cells displaying this alteration |
[29,32,58,59] |
| TERT | Catalytic subunit of the enzyme telomerase | It is present in about 1% of UM cases, whereas it is more common in other cancers TERT promoter mutations lead to the immortalization of somatic cells. Tumours carrying this mutation also showed GNA11 gene alteration. |
[32,60] |
GNAQ (G protein subunit alpha q), GNA11 (G protein subunit alpha 11), CYSLTR2 (cysteinyl leukotriene receptor 2), PLCB4 (phospholipase C, β4), BAP1 (BRCA1-associated protein 1), SF3B1 (splicing factor 3B subunit 1), SRSF2 (serine and arginine rich splicing factor 2), EIF1AX (X-linked eukaryotic translation initiation factor 1A) and TERT (telomerase reverse transcriptase.