GNA11 Q209L Mouse Model Reveals RasGRP3 as an Essential Signaling Node in Uveal Melanoma

• DOI: 10.1016/j.celrep.2018.01.081
• Publication Date: 2018-02-27T16:37:26Z
• Authors: Amanda R. Moore; Leili Ran; Youxin Guan; Jessica J. Sher; Tyler D. Hitchman; Jenny Q. Zhang; Catalina Hwang; Edward G. Walzak; Alexander N. Shou...; Sébastien Monette; Rajmohan Murali; Thomas Wiesner; Klaus G. Griewank; Ping Chi; Yu Chen
• Keywords: GNAQ; BAP1; Melanocyte

Uveal melanoma (UM) is characterized by mutually exclusive activating mutations in GNAQ, GNA11, CYSLTR2, and PLCB4, four genes a linear pathway to activation of PLCβ almost all tumors loss BAP1 the aggressive subset. We generated mice with melanocyte-specific expression GNA11Q209L without homozygous Bap1 loss. The recapitulated human Gq-associated melanomas, they developed pigmented neoplastic lesions from melanocytes skin non-cutaneous organs, including eye leptomeninges, as well at atypical sites, lymph nodes lungs. addition increased tumor proliferation cutaneous size. Integrative transcriptome analysis murine melanomas identified RasGRP3 be specifically expressed GNAQ/GNA11-driven melanomas. In UM cell lines models, required for Ras tumorigenesis. This implicates critical node potential target UM.