Molecular profiling of primary uveal melanoma: results of a Polish cohort

Melanoma Res. 2023 Apr 1;33(2):104-115. doi: 10.1097/CMR.0000000000000874. Epub 2023 Jan 30.


There is no published data regarding the molecular alterations of Polish patients with primary uveal melanoma. We performed whole exome sequencing of 20 primary uveal melanomas (UMs), 10 metastasizing and 10 non-metastasizing cases to identify significant molecular alterations. We detected mutations and copy number variants in the BAP1 gene in 50% (10 cases) of the cases. GNA11 mutations were detected in 50% (10 cases) including nine p.Q209L and one p.R183C. GNAQ mutations gene were detected in 40% (8 cases) and all were p.Q209P. SF3B1, EIF1AX, PLCB4 , and PALB2 mutations were detected in one case each. Genetic aberrations of FBXW7 were detected in 55% of cases, with copy number loss of 10 and missense mutation in one. Gain or loss of copy number was observed in 60%, 60%, and 10% of cases in MYC, MLH1 , and CDKN2A genes, respectively. BAP1 and GNAQ tumor suppressor genes are more often mutated in UM with metastasis, while GNA11 mutations are more frequently detected in non-metastasizing tumors. MYC copy gain was present twice as frequently (80% versus 40%) in cases with versus those without metastases. BAP1 mutation correlated with worse overall survival; while GNA11 mutation and CDKN2A loss correlated with better and worse progression-free survival, respectively. We have confirmed BAP1 prognostic potential and documented frequent MYC amplification in metastasizing cases. Although GNA11 mutation and CDKN2A loss significantly correlated with progression-free survival in our study, our sample size is small. The prognostic significance of GNAQ/GNA11 mutation and CDKN2A loss would require further investigation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Mutational Analysis
  • GTP-Binding Protein alpha Subunits / genetics
  • GTP-Binding Protein alpha Subunits / metabolism
  • GTP-Binding Protein alpha Subunits, Gq-G11 / genetics
  • GTP-Binding Protein alpha Subunits, Gq-G11 / metabolism
  • Humans
  • Melanoma* / pathology
  • Mutation
  • Poland
  • Skin Neoplasms*
  • Ubiquitin Thiolesterase
  • Uveal Neoplasms* / genetics


  • GTP-Binding Protein alpha Subunits
  • GTP-Binding Protein alpha Subunits, Gq-G11
  • Ubiquitin Thiolesterase
  • GNA11 protein, human
  • CDKN2A protein, human

Supplementary concepts

  • Uveal melanoma