FIGURE

Fig. 3

ID

ZDB-FIG-220512-25

Publication

Phelps et al., 2022 - MITF deficiency accelerates GNAQ-driven uveal melanoma

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Fig. 3

A mosaic expression system determines that CYSLTR2^L129Q, YAP^AA, and PLCβ4^D630Y can drive UM tumorigenesis. Mosaic zebrafish are denoted by X➛Y, where X is the gene introduced, and Y is the recipient genotype; Ctl, control GOI–GFP vector; Q, GNAQ^Q209L; C, CYSLTR2 ^L129Q; Q, GNAQ^Q209L; Y, YAP^AA; PLC, PLCB4^D630Y. Germline zebrafish lines and recipient genotypes are as indicated in Figs. 1 and 2. (A) Representative zebrafish images confirm that introduction of GNAQ^Q209L via the GOI–GFP vector results in GFP⁺ pigment patches and tumors. Asterisks and arrows denote pigment patches corresponding to GFP expression. (B) Kaplan–Meier curves show that mosaic zebrafish with control vector or GNAQ^Q209L introduced into pm+ or pm− recipients all have overall survivals that closely mirror their germline pm+, pm−, Qpm+, and Qpm− equivalents (P = n.s.). As with the germline mutants, Q➛pm+ versus Ctl➛pm+ and Q➛pm− versus Ctl➛pm− were both significantly different (P < 0.001, as determined by log-rank test). (C) Kaplan–Meier curves show the effects of mosaic expression of CYSLTR2^L129Q, YAP^AA, and PLCβ4^D630Y in tp53-mutant zebrafish that are either mitfa^+/+ (Left) or mitfa^−/− (Right). Q➛pm+, Q➛pm−, Ctl➛pm+, and Ctl➛pm− data from B are shown for comparison. Statistical significance is as follows: CYSLTR2, C➛pm+ versus Ctl➛pm+ n.s., C➛pm− versus Ctl➛pm− P < 0.0001, as determined by log-rank test; YAP, Y➛pm+ versus Ctl➛pm+ P < 0.0001, Y➛pm− versus Ctl➛pm− P < 0.0001, as determined by log-rank test; PLCβ4, PLC➛pm+ versus Ctl➛pm+ n.s., PLC➛pm− versus Ctl➛pm− P < 0.0001, as determined by log-rank test. (D) Kaplan–Meier curves show that YAP cooperates with mitfa^−/− in a tp53-WT background. Overall survival of Y➛m+ versus YAP➛m−, significant to P < 0.0001, as determined by log-rank test. (E) Kaplan–Meier curves of Q➛Bpm− versus Bpm− controls, with Q➛pm− from B shown for comparison, show that GNAQ^Q209L is dominant over BRAF^V600E in allowing tumors to form the mitfa^−/− background. Statistical significance of overall survival is P < 0.0001 for Q➛Bpm− versus Bpm− and P = 0.0003 for Q➛Bpm− versus Q➛pm−, as determined by log-rank test.

Expression Data

Expression Detail

Antibody Labeling

Phenotype Data

Phenotype Detail

Acknowledgments

This image is the copyrighted work of the attributed author or publisher, and ZFIN has permission only to display this image to its users. Additional permissions should be obtained from the applicable author or publisher of the image. Full text @ Proc. Natl. Acad. Sci. USA