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Functional characterization of uveal melanoma oncogenes

Oncogene volume 40, pages 806–820 (2021)Cite this article

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Abstract

Uveal melanoma (UM) is a currently untreatable form of melanoma with a 50% mortality rate. Characterization of the essential signaling pathways driving this cancer is critical to develop target therapies. Activating mutations in the Gαq signaling pathway at the level of GNAQ, GNA11, or rarely CYSLTR2 or PLCβ4 are considered alterations driving proliferation in UM and several other neoplastic disorders. Here, we systematically examined the oncogenic signaling output of various mutations recurrently identified in human tumors. We demonstrate that CYSLTR2 → GNAQ/11 → PLCβ act in a linear signaling cascade that, via protein kinase C (PKC), activates in parallel the MAP-kinase and FAK/Yes-associated protein pathways. Using genetic ablation and pharmacological inhibition, we show that the PKC/RasGRP3/MAPK signaling branch is the essential component that drives the proliferation of UM. Only inhibition of the MAPK branch but not the FAK branch synergizes with inhibition of the proximal cascade, providing a blueprint for combination therapy. All oncogenic signaling could be extinguished by the novel GNAQ/11 inhibitor YM-254890, in all UM cells with driver mutation in the Gαq subunit or the upstream receptor. Our findings highlight the GNAQ/11 → PLCβ → PKC → MAPK pathway as the central signaling axis to be suppressed pharmacologically to treat for neoplastic disorders with Gαq pathway mutations.

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Fig. 1: Functional characterization of Gαq pathway mutations in UM.
Fig. 2: CYSLTR2, GNAQ/11, and PLCβ act in a linear signaling cascade that activates MAP-kinase via PKC.
Fig. 3: PLCβ activates FAK and MAPK signaling in parallel via PKC.
Fig. 4: PLCβ/PKC activity but not FAK/YAP is elevated in UM cell lines as a consequence of Gαq pathway mutations.
Fig. 5: PKC/MAPK and not FAK/YAP activity is essential for proliferation of UM cells with Gαq pathway mutations.
Fig. 6: Combined inhibition of PKC and MEK but not FAK and MEK or FAK and PKC synergistically reduces cell viability in UM cells.
Fig. 7: YM-254890 selectively suppresses essential oncogenic signaling in GNAQ/11 mutant UM cells.
Fig. 8: YM-254890 selectively inhibits proliferation of melanoma cell lines with Gαq pathway mutations.

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References

  1. Singh AD, Bergman L, Seregard S. Uveal melanoma: epidemiologic aspects. Ophthalmol Clin N Am. 2005;18:75–84.

    Google Scholar 

  2. Arnesen K. The neural crest origin of uveal melanomas. Int Ophthalmol. 1985;7:143–7.

    CAS  PubMed  Google Scholar 

  3. Carvajal RD, Sosman JA, Quevedo JF, Milhem MM, Joshua AM, Kudchadkar RR, et al. Effect of selumetinib vs chemotherapy on progression-free survival in uveal melanoma: a randomized clinical trial. JAMA. 2014;311:2397–405.

    PubMed  PubMed Central  Google Scholar 

  4. Carvajal RD, Piperno-Neumann S, Kapiteijn E, Chapman PB, Frank S, Joshua AM, et al. Selumetinib in combination with dacarbazine in patients with metastatic uveal melanoma: a phase III, multicenter, randomized trial (SUMIT). J Clin Oncol. 2018;36:1232–9.

    CAS  PubMed  Google Scholar 

  5. Piperno-Neumann S, Larkin J, Carvajal RD, Luke JJ, Schwartz GK, Hodi FS, et al. Genomic profiling of metastatic uveal melanoma and clinical results of a phase I study of the protein kinase C inhibitor AEB071. Mol Cancer Ther. 2020;19:1031–9.

    CAS  PubMed  Google Scholar 

  6. Schank TE, Hassel JC. Immunotherapies for the treatment of uveal melanoma-history and future. Cancers. 2019;11:1048.

    PubMed Central  Google Scholar 

  7. Van Raamsdonk CD, Bezrookove V, Green G, Bauer J, Gaugler L, O’Brien JM, et al. Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi. Nature. 2009;457:599–602.

    PubMed  Google Scholar 

  8. Van Raamsdonk CD, Griewank KG, Crosby MB, Garrido MC, Vemula S, Wiesner T, et al. Mutations in GNA11 in uveal melanoma. N Engl J Med. 2010;363:2191–9.

    PubMed  PubMed Central  Google Scholar 

  9. Robertson AG, Shih J, Yau C, Gibb EA, Oba J, Mungall KL, et al. Integrative analysis identifies four molecular and clinical subsets in uveal melanoma. Cancer Cell. 2017;32:204–20.e15.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Schneider B, Riedel K, Zhivov A, Huehns M, Zettl H, Guthoff RF. Frequent and yet unreported GNAQ and GNA11 mutations are found in uveal melanomas. Pathol Oncol Res. 2019;25:1319–25.

    CAS  PubMed  Google Scholar 

  11. Maziarz M, Leyme A, Marivin A, Luebbers A, Patel PP, Chen Z, et al. Atypical activation of the G protein Galphaq by the oncogenic mutation Q209P. J Biol Chem. 2018;293:19586–99.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Moore AR, Ceraudo E, Sher JJ, Guan Y, Shoushtari AN, Chang MT, et al. Recurrent activating mutations of G-protein-coupled receptor CYSLTR2 in uveal melanoma. Nat Genet. 2016;48:675–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Johansson P, Aoude LG, Wadt K, Glasson WJ, Warrier SK, Hewitt AW, et al. Deep sequencing of uveal melanoma identifies a recurrent mutation in PLCB4. Oncotarget. 2016;7:4624–31.

    PubMed  Google Scholar 

  14. Sheng X, Kong Y, Li Y, Zhang Q, Si L, Cui C, et al. GNAQ and GNA11 mutations occur in 9.5% of mucosal melanoma and are associated with poor prognosis. Eur J Cancer. 2016;65:156–63.

    CAS  PubMed  Google Scholar 

  15. Murali R, Wiesner T, Rosenblum MK, Bastian BC. GNAQ and GNA11 mutations in melanocytomas of the central nervous system. Acta Neuropathol. 2012;123:457–9.

    PubMed  PubMed Central  Google Scholar 

  16. Thomas AC, Zeng Z, Riviere JB, O’Shaughnessy R, Al-Olabi L, St-Onge J, et al. Mosaic activating mutations in GNA11 and GNAQ are associated with phakomatosis pigmentovascularis and extensive dermal melanocytosis. J Invest Dermatol. 2016;136:770–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Ayturk UM, Couto JA, Hann S, Mulliken JB, Williams KL, Huang AY, et al. Somatic activating mutations in GNAQ and GNA11 are associated with congenital hemangioma. Am J Hum Genet. 2016;98:789–95.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Bean GR, Joseph NM, Gill RM, Folpe AL, Horvai AE, Umetsu SE. Recurrent GNAQ mutations in anastomosing hemangiomas. Mod Pathol. 2017;30:722–7.

    CAS  PubMed  Google Scholar 

  19. Couto JA, Ayturk UM, Konczyk DJ, Goss JA, Huang AY, Hann S, et al. A somatic GNA11 mutation is associated with extremity capillary malformation and overgrowth. Angiogenesis. 2017;20:303–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Couto JA, Huang L, Vivero MP, Kamitaki N, Maclellan RA, Mulliken JB, et al. Endothelial cells from capillary malformations are enriched for somatic GNAQ mutations. Plast Reconstr Surg. 2016;137:77e–82e.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Joseph NM, Brunt EM, Marginean C, Nalbantoglu I, Snover DC, Thung SN, et al. Frequent GNAQ and GNA14 mutations in hepatic small vessel neoplasm. Am J Surg Pathol. 2018;42:1201–7.

    PubMed  Google Scholar 

  22. Nakashima M, Miyajima M, Sugano H, Iimura Y, Kato M, Tsurusaki Y, et al. The somatic GNAQ mutation c.548G>A (p.R183Q) is consistently found in Sturge-Weber syndrome. J Hum Genet. 2014;59:691–3.

    CAS  PubMed  Google Scholar 

  23. Shirley MD, Tang H, Gallione CJ, Baugher JD, Frelin LP, Cohen B, et al. Sturge-Weber syndrome and port-wine stains caused by somatic mutation in GNAQ. N Engl J Med. 2013;368:1971–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Shain AH, Bagger MM, Yu R, Chang D, Liu S, Vemula S, et al. The genetic evolution of metastatic uveal melanoma. Nat Genet. 2019;51:1123–30.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Furney SJ, Pedersen M, Gentien D, Dumont AG, Rapinat A, Desjardins L, et al. SF3B1 mutations are associated with alternative splicing in uveal melanoma. Cancer Discov. 2013;3:1122–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Harbour JW, Roberson ED, Anbunathan H, Onken MD, Worley LA, Bowcock AM. Recurrent mutations at codon 625 of the splicing factor SF3B1 in uveal melanoma. Nat Genet. 2013;45:133–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Martin M, Masshofer L, Temming P, Rahmann S, Metz C, Bornfeld N, et al. Exome sequencing identifies recurrent somatic mutations in EIF1AX and SF3B1 in uveal melanoma with disomy 3. Nat Genet. 2013;45:933–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Harbour JW, Onken MD, Roberson ED, Duan S, Cao L, Worley LA, et al. Frequent mutation of BAP1 in metastasizing uveal melanomas. Science. 2010;330:1410–3.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Rhee SG, Bae YS. Regulation of phosphoinositide-specific phospholipase C isozymes. J Biol Chem. 1997;272:15045–8.

    CAS  PubMed  Google Scholar 

  30. Teixeira C, Stang SL, Zheng Y, Beswick NS, Stone JC. Integration of DAG signaling systems mediated by PKC-dependent phosphorylation of RasGRP3. Blood. 2003;102:1414–20.

    CAS  PubMed  Google Scholar 

  31. Goldsmith ZG, Dhanasekaran DN. G protein regulation of MAPK networks. Oncogene. 2007;26:3122–42.

    CAS  PubMed  Google Scholar 

  32. Chen X, Wu Q, Depeille P, Chen P, Thornton S, Kalirai H, et al. RasGRP3 mediates MAPK pathway activation in GNAQ mutant uveal melanoma. Cancer Cell. 2017;31:685–96.e6.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Chen X, Wu Q, Tan L, Porter D, Jager MJ, Emery C, et al. Combined PKC and MEK inhibition in uveal melanoma with GNAQ and GNA11 mutations. Oncogene. 2014;33:4724–34.

    CAS  PubMed  Google Scholar 

  34. Moore AR, Ran L, Guan Y, Sher JJ, Hitchman TD, Zhang JQ, et al. GNA11 Q209L mouse model reveals RasGRP3 as aN Essential Signaling Node in Uveal Melanoma. Cell Rep. 2018;22:2455–68.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Yu FX, Luo J, Mo JS, Liu G, Kim YC, Meng Z, et al. Mutant Gq/11 promote uveal melanoma tumorigenesis by activating YAP. Cancer Cell. 2014;25:822–30.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Feng X, Degese MS, Iglesias-Bartolome R, Vaque JP, Molinolo AA, Rodrigues M, et al. Hippo-independent activation of YAP by the GNAQ uveal melanoma oncogene through a trio-regulated rho GTPase signaling circuitry. Cancer Cell. 2014;25:831–45.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Feng X, Arang N, Rigiracciolo DC, Lee JS, Yeerna H, Wang Z, et al. A platform of synthetic lethal gene interaction networks reveals that the GNAQ uveal melanoma oncogene controls the Hippo pathway through FAK. Cancer Cell. 2019;35:457–72.e5.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Annala S, Feng X, Shridhar N, Eryilmaz F, Patt J, Yang J. et al. Direct targeting of Galphaq and Galpha11 oncoproteins in cancer cells. Sci Signal. 2019;12:eaau5948.

    PubMed  Google Scholar 

  39. Trinquet E, Fink M, Bazin H, Grillet F, Maurin F, Bourrier E, et al. D-myo-inositol 1-phosphate as a surrogate of D-myo-inositol 1,4,5-tris phosphate to monitor G protein-coupled receptor activation. Anal Biochem. 2006;358:126–35.

    CAS  PubMed  Google Scholar 

  40. Rozengurt E, Rey O, Waldron RT. Protein kinase D signaling. J Biol Chem. 2005;280:13205–8.

    CAS  PubMed  Google Scholar 

  41. Takasaki J, Saito T, Taniguchi M, Kawasaki T, Moritani Y, Hayashi K, et al. A novel Galphaq/11-selective inhibitor. J Biol Chem. 2004;279:47438–45.

    CAS  PubMed  Google Scholar 

  42. Kamato D, Thach L, Bernard R, Chan V, Zheng W, Kaur H, et al. Structure, function, pharmacology, and therapeutic potential of the G protein, Galpha/q,11. Front Cardiovasc Med. 2015;2:14.

    PubMed  PubMed Central  Google Scholar 

  43. Wilkie TM, Scherle PA, Strathmann MP, Slepak VZ, Simon MI. Characterization of G-protein alpha subunits in the Gq class: expression in murine tissues and in stromal and hematopoietic cell lines. Proc Natl Acad Sci USA. 1991;88:10049–53.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Lim YH, Bacchiocchi A, Qiu J, Straub R, Bruckner A, Bercovitch L, et al. GNA14 somatic mutation causes congenital and sporadic vascular tumors by MAPK activation. Am J Hum Genet. 2016;99:443–50.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Heasley LE, Storey B, Fanger GR, Butterfield L, Zamarripa J, Blumberg D, et al. GTPase-deficient G alpha 16 and G alpha q induce PC12 cell differentiation and persistent activation of cJun NH2-terminal kinases. Mol Cell Biol. 1996;16:648–56.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Masters SB, Miller RT, Chi MH, Chang FH, Beiderman B, Lopez NG, et al. Mutations in the GTP-binding site of GS alpha alter stimulation of adenylyl cyclase. J Biol Chem. 1989;264:15467–74.

    CAS  PubMed  Google Scholar 

  47. Ellen Kapiteijn MC, Boni V, Loirat D, Speetjens F, Park J, Calvo E, et al. A phase I trial of LXS196, a novel PKC inhibitor for metastatic uveal melanoma. Cancer Res. 2019;79 13 Suppl:Abstract nr CT068. 2019.

  48. Tanjoni I, Walsh C, Uryu S, Tomar A, Nam JO, Mielgo A, et al. PND-1186 FAK inhibitor selectively promotes tumor cell apoptosis in three-dimensional environments. Cancer Biol Ther. 2010;9:764–77.

    CAS  PubMed  Google Scholar 

  49. Dong J, Feldmann G, Huang J, Wu S, Zhang N, Comerford SA, et al. Elucidation of a universal size-control mechanism in Drosophila and mammals. Cell. 2007;130:1120–33.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Zhao B, Wei X, Li W, Udan RS, Yang Q, Kim J, et al. Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control. Genes Dev. 2007;21:2747–61.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Hao Y, Chun A, Cheung K, Rashidi B, Yang X. Tumor suppressor LATS1 is a negative regulator of oncogene YAP. J Biol Chem. 2008;283:5496–509.

    CAS  PubMed  Google Scholar 

  52. Levy D, Adamovich Y, Reuven N, Shaul Y. Yap1 phosphorylation by c-Abl is a critical step in selective activation of proapoptotic genes in response to DNA damage. Mol Cell. 2008;29:350–61.

    CAS  PubMed  Google Scholar 

  53. Li B, He J, Lv H, Liu Y, Lv X, Zhang C, et al. c-Abl regulates YAPY357 phosphorylation to activate endothelial atherogenic responses to disturbed flow. J Clin Investig. 2019;129:1167–79.

    PubMed  PubMed Central  Google Scholar 

  54. Sugihara T, Werneburg NW, Hernandez MC, Yang L, Kabashima A, Hirsova P, et al. YAP tyrosine phosphorylation and nuclear localization in cholangiocarcinoma cells are regulated by LCK and independent of LATS activity. Mol Cancer Res. 2018;16:1556–67.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Cao J, Wu L, Zhang SM, Lu M, Cheung WK, Cai W, et al. An easy and efficient inducible CRISPR/Cas9 platform with improved specificity for multiple gene targeting. Nucleic Acids Res. 2016;44:e149.

    PubMed  PubMed Central  Google Scholar 

  56. Di Veroli GY, Fornari C, Wang D, Mollard S, Bramhall JL, Richards FM, et al. Combenefit: an interactive platform for the analysis and visualization of drug combinations. Bioinformatics. 2016;32:2866–8.

    PubMed  PubMed Central  Google Scholar 

  57. van Dinten LC, Pul N, van Nieuwpoort AF, Out CJ, Jager MJ, van den Elsen PJ. Uveal and cutaneous melanoma: shared expression characteristics of melanoma-associated antigens. Investig Ophthalmol Vis Sci. 2005;46:24–30.

    Google Scholar 

  58. Martins L, Giovani PA, Reboucas PD, Brasil DM, Haiter Neto F, Coletta RD, et al. Computational analysis for GNAQ mutations: new insights on the molecular etiology of Sturge-Weber syndrome. J Mol Graph Model. 2017;76:429–40.

    CAS  PubMed  Google Scholar 

  59. Kostenis E, Pfeil EM, Annala S. Heterotrimeric Gq proteins as therapeutic targets? J Biol Chem. 2020;295:5206–15.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Jhon DY, Lee HH, Park D, Lee CW, Lee KH, Yoo OJ, et al. Cloning, sequencing, purification, and Gq-dependent activation of phospholipase C-beta 3. J Biol Chem. 1993;268:6654–61.

    CAS  PubMed  Google Scholar 

  61. Lee CW, Lee KH, Lee SB, Park D, Rhee SG. Regulation of phospholipase C-beta 4 by ribonucleotides and the alpha subunit of Gq. J Biol Chem. 1994;269:25335–8.

    CAS  PubMed  Google Scholar 

  62. Lee CH, Park D, Wu D, Rhee SG, Simon MI. Members of the Gq alpha subunit gene family activate phospholipase C beta isozymes. J Biol Chem. 1992;267:16044–7.

    CAS  PubMed  Google Scholar 

  63. Kim YJ, Lee SC, Kim SE, Kim SH, Kim SK, Lee CS. YAP activity is not associated with survival of uveal melanoma patients and cell lines. Sci Rep. 2020;10:6209.

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Schrage R, Schmitz AL, Gaffal E, Annala S, Kehraus S, Wenzel D, et al. The experimental power of FR900359 to study Gq-regulated biological processes. Nat Commun. 2015;6:10156.

    CAS  PubMed  Google Scholar 

  65. Lapadula D, Farias E, Randolph CE, Purwin TJ, McGrath D, Charpentier TH, et al. Effects of oncogenic Galphaq and Galpha11 inhibition by FR900359 in uveal melanoma. Mol Cancer Res. 2019;17:963–73.

    CAS  PubMed  Google Scholar 

  66. Onken MD, Makepeace CM, Kaltenbronn KM, Kanai SM, Todd TD, Wang S. Targeting nucleotide exchange to inhibit constitutively active G protein alpha subunits in cancer cells. Sci Signal. 2018;11:eaao6852.

    PubMed  PubMed Central  Google Scholar 

  67. Tietze D, Kaufmann D, Tietze AA, Voll A, Reher R, Konig G, et al. Structural and dynamical basis of G protein inhibition by YM-254890 and FR900359: an inhibitor in action. J Chem Inf Model. 2019;59:4361–73.

    CAS  PubMed  Google Scholar 

  68. Malfacini D, Patt J, Annala S, Harpsoe K, Eryilmaz F, Reher R, et al. Rational design of a heterotrimeric G protein alpha subunit with artificial inhibitor sensitivity. J Biol Chem. 2019;294:5747–58.

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Kuschak M, Namasivayam V, Rafehi M, Voss JH, Garg J, Schlegel JG, et al. Cell-permeable high-affinity tracers for Gq proteins provide structural insights, reveal distinct binding kinetics and identify small molecule inhibitors. Br J Pharmacol. 2020;177:1898–916.

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Sanjana NE, Shalem O, Zhang F. Improved vectors and genome-wide libraries for CRISPR screening. Nat Methods. 2014;11:783–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Griewank KG, Yu X, Khalili J, Sozen MM, Stempke-Hale K, Bernatchez C, et al. Genetic and molecular characterization of uveal melanoma cell lines. Pigment Cell Melanoma Res. 2012;25:182–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Amirouchene-Angelozzi N, Nemati F, Gentien D, Nicolas A, Dumont A, Carita G, et al. Establishment of novel cell lines recapitulating the genetic landscape of uveal melanoma and preclinical validation of mTOR as a therapeutic target. Mol Oncol. 2014;8:1508–20.

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2012;2:401–4.

    PubMed  Google Scholar 

  74. Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO, et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal. 2013;6:pl1.

    PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by R35 grant CA220481 and R01 grant CA142873 from the National Cancer Institute and the Gerson and Barbara Baker Distinguished Professorship (all to BCB). We thank Han Yue for providing help for IP1 assay. We thank the Preclinical Therapeutics, Laboratory for Cell Analysis of University of California, San Francisco for technical support and analyses.

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  1. Departments of Dermatology and Pathology and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, 94143, USA

    Jiafang Ma, Li Weng, Boris C. Bastian & Xu Chen

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  1. Jiafang Ma
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BCB and XC supervised the study and wrote the paper. JM and XC performed all experiments except YAP1 CRSPR/Cas9 knockout was performed by LW. All authors reviewed the paper.

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Correspondence to Boris C. Bastian or Xu Chen.

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Ma, J., Weng, L., Bastian, B.C. et al. Functional characterization of uveal melanoma oncogenes. Oncogene 40, 806–820 (2021). https://doi.org/10.1038/s41388-020-01569-5

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