Abstract 42P
Background
Uveal melanoma (UM) is the most common cancer of the eye. Previous research has identified three key driver mutations in UM tumorigenesis: 1) gain of function Gq signaling pathway mutations, 2) BAP1 loss of function mutations, and 3) aberrant expression of PRAME. However, the combined impact of these aberrations is not known. The purpose of this study was to characterize the phenotype of uveal melanocytes harboring one or more of these aberrations.
Methods
Uveal melanocytes were isolated from adult and neonatal murine choroid and were genetically engineered to express one or more of the three canonical aberrations. Phenotypic and transcriptional assays were performed to assess phenotypic changes.
Results
The stepwise addition of these aberrations resulted in progressive deregulation of transcriptome, morphology, and growth properties resembling findings in human uveal melanoma.
Conclusions
This unique genetically engineered mouse uveal melanocyte model will be invaluable for understanding how the progressive genetic evolution of human uveal melanoma results in increased malignant propensity.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
J. William Harbour.
Funding
Melanoma Research Foundation.
Disclosure
All authors have declared no conflicts of interest.