Uveal melanoma driver mutations in GNAQ/11 yield numerous changes in melanocyte biology.

ABSTRACT: Uveal melanoma (UM) is the most common primary intraocular cancer and has a high incidence of metastasis, which lacks any effective treatment. Here, we present zebrafish models of UM, which are driven by melanocyte-specific expression of activating GNAQ or GNA11 alleles, GNAQ/11^Q209L , the predominant initiating mutations for human UM. When combined with mutant tp53, GNAQ/11^Q209L transgenics develop various melanocytic tumors, including UM, with near complete penetrance. These tumors display nuclear YAP localization and thus phenocopy human UM. We show that GNAQ/11^Q209L expression induces profound melanocyte defects independent of tp53 mutation, which are apparent within 3 days of development. First, increases in melanocyte number, melanin content, and subc

SUBMITTER: Perez DE 

PROVIDER: S-EPMC6151293 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature