Background: Mutations in GNAQ/11 genes are considered an early event in the development of uveal melanoma that may derive from a pre-existing nevus. The Hippo pathway, by way of YAP activation, rather than MAP kinase, has a role in the oncogenic capacity of GNAQ/11 mutations.Methods: We investigated 16 nevi from 13 human eyes for driver GNAQ/11 mutations using droplet digital PCR and determined whether nevi are clonal by quantifying mutant nevus cell fractions. Immunohistochemistry was performed on 15 nevi to analyse YAP activation.Results: For 15 out of 16 nevi, a GNAQ/11 mutation was detected in the nevus cells albeit at a low frequency with a median of 13%. Nuclear YAP, a transcriptional co-activator in the Hippo tumour-suppressor pathway, was detected in 14/15 nevi.Conclusions: Our analysis suggests that a mutation in GNAQ/11 occurs in a subset of choroidal nevus cells. We hypothesise that GNAQ/11 mutant-driven extracellular mitogenic signalling involving YAP activation leads to accumulation of wild-type nevus cells.

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Journal British Journal of Cancer
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Vader, M.J.C. (M. J.C.), Madigan, M.C. (M. C.), Versluis, M, Suleiman, H.M. (H. M.), Gezgin, G, Gruis, N.A, … van der Velden, P.A. (2017). GNAQ and GNA11 mutations and downstream YAP activation in choroidal nevi. British Journal of Cancer, 117(6), 884–887. doi:10.1038/bjc.2017.259