A multi-step immune-competent genetic mouse model reveals phenotypic plasticity in uveal melanoma.

ABSTRACT: Uveal melanoma (UM) is a highly aggressive intraocular malignancy with limited therapeutic options for metastatic disease. Existing transgenic UM mouse models inadequately recapitulate human disease progression, while transplant models lack immune competence for studying the tumor immune microenvironment and therapeutic interventions. To address these limitations, we developed a genetically engineered mouse model incorporating stepwise genetic alterations implicated in human UM progression. Spatiotemporally controlled expression of mutant GNAQ^Q209L from the endogenous locus induced choroidal nevi with limited penetrance. Concomitant BAP1 deletion enhanced nevus formation, while further MYC activation led to fully penetrant intraocular tumors with metastatic potential. Single-cel

SUBMITTER: Xu X 

PROVIDER: S-EPMC12157397 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature