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Genetics of Uveal Melanoma

  • Helen Kalirai
  • Alexander Iu. Tsygankov
  • Sophie Thornton
  • Svetlana V. Saakyan
  • Sarah E. CouplandEmail author
Chapter
First Online:

Abstract

Uveal melanoma is a rare, aggressive intraocular malignant tumor, leading to metastatic disease in over 50% of patients with tumors located in the ciliary body or choroid. Genetic studies have identified chromosomal changes, mutations and gene expression profiles linked to both tumour development and progression. In this chapter we present the current knowledge surrounding these key molecular changes, how they are being used to predict metastatic risk, their functional relevance to tumor biology and how they may inform the identification of therapeutic targets to treat metastatic disease.

Keywords

Uveal melanoma Genetics Monosomy 3 GNAQ GNA11 BAP1 EIF1AX SF3B1 
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References

  1. 1.
    Damato BE, Coupland SE. Differences in uveal melanomas between men and women from the British Isles. Eye (Lond). 2012;26(2):292–9.CrossRefGoogle Scholar
  2. 2.
    Khan S, Finger PT, Yu GP, Razzaq L, Jager MJ, de Keizer RJ, et al. Clinical and pathologic characteristics of biopsy-proven iris melanoma: a multicenter international study. Arch Ophthalmol. 2012;130(1):57–64.PubMedCrossRefPubMedCentralGoogle Scholar
  3. 3.
    Krishna Y, Kalirai H, Thornton S, Damato BE, Heimann H, Coupland SE. Genetic findings in treatment-naive and proton-beam-radiated iris melanomas. Br J Ophthalmol. 2016;100(7):1012–6.PubMedCrossRefPubMedCentralGoogle Scholar
  4. 4.
    Caines R, Eleuteri A, Kalirai H, Fisher AC, Heimann H, Damato BE, et al. Cluster analysis of multiplex ligation-dependent probe amplification data in choroidal melanoma. Mol Vis. 2015;21:1–11.PubMedCentralGoogle Scholar
  5. 5.
    Coupland SE, Lake SL, Zeschnigk M, Damato BE. Molecular pathology of uveal melanoma. Eye (Lond). 2013;27(2):230–42.CrossRefGoogle Scholar
  6. 6.
    Harbour JW. A prognostic test to predict the risk of metastasis in uveal melanoma based on a 15-gene expression profile. Methods Mol Biol. 2014;1102:427–40.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Carvajal RD. Update on the treatment of uveal melanoma. Clin Adv Hematol Oncol. 2016;14(10):768–70.PubMedGoogle Scholar
  8. 8.
    Carvajal RD, Schwartz GK, Tezel T, Marr B, Francis JH, Nathan PD. Metastatic disease from uveal melanoma: treatment options and future prospects. Br J Ophthalmol. 2017;101(1):38–44.CrossRefGoogle Scholar
  9. 9.
    Woodman SE. Metastatic uveal melanoma: biology and emerging treatments. Cancer J. 2012;18(2):148–52.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Carvajal RD, Yavuzyigitoglu S, Drabarek W, Smit KN, van Poppelen N, Koopmans AE, et al. Update on the treatment of uveal melanoma. Clin Adv Hematol Oncol. 2016;14(10):768–70.PubMedGoogle Scholar
  11. 11.
    Damato B, Dopierala JA, Coupland SE. Genotypic profiling of 452 choroidal melanomas with multiplex ligation-dependent probe amplification. Clin Cancer Res. 2010;16(24):6083–92.PubMedCrossRefGoogle Scholar
  12. 12.
    Ehlers JP, Worley L, Onken MD, Harbour JW. Integrative genomic analysis of aneuploidy in uveal melanoma. Clin Cancer Res. 2008;14(1):115–22.PubMedCrossRefGoogle Scholar
  13. 13.
    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(2):204–20.e15.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    de Lange MJ, van Pelt SI, Versluis M, Jordanova ES, Kroes WG, Ruivenkamp C, et al. Heterogeneity revealed by integrated genomic analysis uncovers a molecular switch in malignant uveal melanoma. Oncotarget. 2015;6(35):37824–35.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Ehlers JP, Harbour JW. Molecular pathobiology of uveal melanoma. Int Ophthalmol Clin. 2006;46(1):167–80.PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Kilic E, van Gils W, Lodder E, Beverloo HB, van Til ME, Mooy CM, et al. Clinical and cytogenetic analyses in uveal melanoma. Invest Ophthalmol Vis Sci. 2006;47(9):3703–7.PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Singh N, Singh AD, Hide W. Inferring an evolutionary tree of uveal melanoma from genomic copy number aberrations. Invest Ophthalmol Vis Sci. 2015;56(11):6801–9.PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Damato B, Eleuteri A, Taktak AF, Coupland SE. Estimating prognosis for survival after treatment of choroidal melanoma. Prog Retin Eye Res. 2011;30(5):285–95.PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Dogrusoz M, Bagger M, van Duinen SG, Kroes WG, Ruivenkamp CA, Bohringer S, et al. The prognostic value of AJCC staging in uveal melanoma is enhanced by adding chromosome 3 and 8q status. Invest Ophthalmol Vis Sci. 2017;58(2):833–42.PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Eleuteri A, Damato B, Coupland SE, Taktak A. Enhancing survival prognostication in patients with choroidal melanoma by integrating pathologic, clinical and genetic predictors of metastasis. Int J Biomed Eng Technol. 2012;8(1):18–35.CrossRefGoogle Scholar
  21. 21.
    DeParis SW, Taktak A, Eleuteri A, Enanoria W, Heimann H, Coupland SE, et al. External validation of the liverpool uveal melanoma prognosticator online. Invest Ophthalmol Vis Sci. 2016;57(14):6116–22.PubMedCrossRefGoogle Scholar
  22. 22.
    Vaquero-Garcia J, Lalonde E, Ewens KG, Ebrahimzadeh J, Richard-Yutz J, Shields CL, et al. PRiMeUM: a model for predicting risk of metastasis in uveal melanoma. Invest Ophthalmol Vis Sci. 2017;58(10):4096–105.PubMedCentralCrossRefPubMedGoogle Scholar
  23. 23.
    Coupland SE, Damato BE. Molecular analysis of uveal melanoma. Ophthalmology. 2013;120(7):e50.PubMedCrossRefGoogle Scholar
  24. 24.
    Tschentscher F, Prescher G, Zeschnigk M, Horsthemke B, Lohmann DR. Identification of chromosomes 3, 6, and 8 aberrations in uveal melanoma by microsatellite analysis in comparison to comparative genomic hybridization. Cancer Genet Cytogenet. 2000;122(1):13–7.PubMedCrossRefGoogle Scholar
  25. 25.
    Hussain RN, Kalirai H, Groenewald C, Kacperek A, Errington RD, Coupland SE, et al. Prognostic biopsy of choroidal melanoma after proton beam radiation therapy. Ophthalmology. 2016;123(10):2264–5.PubMedCrossRefGoogle Scholar
  26. 26.
    Onken MD, Worley LA, Ehlers JP, Harbour JW. Gene expression profiling in uveal melanoma reveals two molecular classes and predicts metastatic death. Cancer Res. 2004;64(20):7205–9.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Tschentscher F, Husing J, Holter T, Kruse E, Dresen IG, Jockel KH, et al. Tumor classification based on gene expression profiling shows that uveal melanomas with and without monosomy 3 represent two distinct entities. Cancer Res. 2003;63(10):2578–84.PubMedGoogle Scholar
  28. 28.
    Zuidervaart W, van der Velden PA, Hurks MH, van Nieuwpoort FA, Out-Luiting CJ, Singh AD, et al. Gene expression profiling identifies tumour markers potentially playing a role in uveal melanoma development. Br J Cancer. 2003;89(10):1914–9.PubMedCentralCrossRefPubMedGoogle Scholar
  29. 29.
    Chang SH, Worley LA, Onken MD, Harbour JW. Prognostic biomarkers in uveal melanoma: evidence for a stem cell-like phenotype associated with metastasis. Melanoma Res. 2008;18(3):191–200.PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    Field MG, Harbour JW. Recent developments in prognostic and predictive testing in uveal melanoma. Curr Opin Ophthalmol. 2014;25(3):234–9.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Field MG, Durante MA, Decatur CL, Tarlan B, Oelschlager KM, Stone JF, et al. Epigenetic reprogramming and aberrant expression of PRAME are associated with increased metastatic risk in Class 1 and Class 2 uveal melanomas. Oncotarget. 2016;7(37):59209–19.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Onken MD, Worley LA, Char DH, Augsburger JJ, Correa ZM, Nudleman E, et al. Collaborative Ocular Oncology Group report number 1: prospective validation of a multi-gene prognostic assay in uveal melanoma. Ophthalmology. 2012;119(8):1596–603.PubMedCentralCrossRefPubMedGoogle Scholar
  33. 33.
    Decatur CL, Ong E, Garg N, Anbunathan H, Bowcock AM, Field MG, et al. Driver mutations in uveal melanoma: associations with gene expression profile and patient outcomes. JAMA Ophthalmol. 2016;134(7):728–33.PubMedCentralCrossRefPubMedGoogle Scholar
  34. 34.
    Dono M, Angelini G, Cecconi M, Amaro A, Esposito AI, Mirisola V, et al. Mutation frequencies of GNAQ, GNA11, BAP1, SF3B1, EIF1AX and TERT in uveal melanoma: detection of an activating mutation in the TERT gene promoter in a single case of uveal melanoma. Br J Cancer. 2014;110(4):1058–65.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    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(6009):1410–3.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    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(2):133–5.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    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(8):933–6.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Royer-Bertrand B, Torsello M, Rimoldi D, El Zaoui I, Cisarova K, Pescini-Gobert R, et al. Comprehensive genetic landscape of uveal melanoma by whole-genome sequencing. Am J Hum Genet. 2016;99(5):1190–8.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    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(7229):599–602.CrossRefPubMedGoogle Scholar
  40. 40.
    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(23):2191–9.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Yavuzyigitoglu S, Drabarek W, Smit KN, van Poppelen N, Koopmans AE, Vaarwater J, et al. Correlation of gene mutation status with copy number profile in uveal melanoma. Ophthalmology. 2017;124(4):573–5.PubMedCrossRefPubMedCentralGoogle Scholar
  42. 42.
    Yavuzyigitoglu S, Koopmans AE, Verdijk RM, Vaarwater J, Eussen B, van Bodegom A, et al. Uveal melanomas with SF3B1 mutations: a distinct subclass associated with late-onset metastases. Ophthalmology. 2016;123(5):1118–28.PubMedCrossRefPubMedCentralGoogle Scholar
  43. 43.
    Onken MD, Worley LA, Long MD, Duan S, Council ML, Bowcock AM, et al. Oncogenic mutations in GNAQ occur early in uveal melanoma. Invest Ophthalmol Vis Sci. 2008;49(12):5230–4.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Scholz SL, Moller I, Reis H, Susskind D, van de Nes JAP, Leonardelli S, et al. Frequent GNAQ, GNA11, and EIF1AX mutations in iris melanoma. Invest Ophthalmol Vis Sci. 2017;58(9):3464–70.PubMedCrossRefPubMedCentralGoogle Scholar
  45. 45.
    Mudhar HS, Doherty R, Salawu A, Sisley K, Rennie IG. Immunohistochemical and molecular pathology of ocular uveal melanocytoma: evidence for somatic GNAQ mutations. Br J Ophthalmol. 2013;97(7):924–8.CrossRefGoogle Scholar
  46. 46.
    Vader MJC, Madigan MC, Versluis M, Suleiman HM, Gezgin G, Gruis NA, et al. GNAQ and GNA11 mutations and downstream YAP activation in choroidal nevi. Br J Cancer. 2017;117(6):884–7.PubMedCentralCrossRefGoogle Scholar
  47. 47.
    Metz CH, Scheulen M, Bornfeld N, Lohmann D, Zeschnigk M. Ultradeep sequencing detects GNAQ and GNA11 mutations in cell-free DNA from plasma of patients with uveal melanoma. Cancer Med. 2013;2(2):208–15.PubMedCentralCrossRefGoogle Scholar
  48. 48.
    Shoushtari AN, Carvajal RD. GNAQ and GNA11 mutations in uveal melanoma. Melanoma Res. 2014;24(6):525–34.PubMedCrossRefGoogle Scholar
  49. 49.
    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(5):685–96.e6.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Ambrosini G, Pratilas CA, Qin LX, Tadi M, Surriga O, Carvajal RD, et al. Identification of unique MEK-dependent genes in GNAQ mutant uveal melanoma involved in cell growth, tumor cell invasion, and MEK resistance. Clin Cancer Res. 2012;18(13):3552–61.PubMedCentralCrossRefGoogle Scholar
  51. 51.
    Amirouchene-Angelozzi N, Frisch-Dit-Leitz E, Carita G, Dahmani A, Raymondie C, Liot G, et al. The mTOR inhibitor Everolimus synergizes with the PI3K inhibitor GDC0941 to enhance anti-tumor efficacy in uveal melanoma. Oncotarget. 2016;7(17):23633–46.PubMedCentralCrossRefGoogle Scholar
  52. 52.
    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(39):4724–34.PubMedCrossRefPubMedCentralGoogle Scholar
  53. 53.
    Ho AL, Musi E, Ambrosini G, Nair JS, Deraje Vasudeva S, de Stanchina E, et al. Impact of combined mTOR and MEK inhibition in uveal melanoma is driven by tumor genotype. PLoS One. 2012;7(7):e40439.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Khalili JS, Yu X, Wang J, Hayes BC, Davies MA, Lizee G, et al. Combination small molecule MEK and PI3K inhibition enhances uveal melanoma cell death in a mutant GNAQ- and GNA11-dependent manner. Clin Cancer Res. 2012;18(16):4345–55.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Musi E, Ambrosini G, de Stanchina E, Schwartz GK. The phosphoinositide 3-kinase alpha selective inhibitor BYL719 enhances the effect of the protein kinase C inhibitor AEB071 in GNAQ/GNA11-mutant uveal melanoma cells. Mol Cancer Ther. 2014;13(5):1044–53.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Komatsubara KM, Manson DK, Carvajal RD. Selumetinib for the treatment of metastatic uveal melanoma: past and future perspectives. Future Oncol. 2016;12(11):1331–44.PubMedCrossRefPubMedCentralGoogle Scholar
  57. 57.
    Luke JJ, Triozzi PL, McKenna KC, Van Meir EG, Gershenwald JE, Bastian BC, et al. Biology of advanced uveal melanoma and next steps for clinical therapeutics. Pigment Cell Melanoma Res. 2015;28(2):135–47.CrossRefGoogle Scholar
  58. 58.
    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(6):831–45.PubMedCentralCrossRefGoogle Scholar
  59. 59.
    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(6):822–30.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Yoo JH, Shi DS, Grossmann AH, Sorensen LK, Tong Z, Mleynek TM, et al. ARF6 is an actionable node that orchestrates oncogenic GNAQ signaling in uveal melanoma. Cancer Cell. 2016;29(6):889–904.PubMedCentralCrossRefGoogle Scholar
  61. 61.
    Ewens KG, Kanetsky PA, Richards-Yutz J, Purrazzella J, Shields CL, Ganguly T, et al. Chromosome 3 status combined with BAP1 and EIF1AX mutation profiles are associated with metastasis in uveal melanoma. Invest Ophthalmol Vis Sci. 2014;55(8):5160–7.PubMedCrossRefPubMedCentralGoogle Scholar
  62. 62.
    van Essen TH, van Pelt SI, Versluis M, Bronkhorst IH, van Duinen SG, Marinkovic M, et al. Prognostic parameters in uveal melanoma and their association with BAP1 expression. Br J Ophthalmol. 2014;98(12):1738–43.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Yavuzyigitoglu S, Mensink HW, Smit KN, Vaarwater J, Verdijk RM, Beverloo B, et al. Metastatic disease in polyploid uveal melanoma patients is associated with BAP1 mutations. Invest Ophthalmol Vis Sci. 2016;57(4):2232–9.PubMedCrossRefPubMedCentralGoogle Scholar
  64. 64.
    Jensen DE, Rauscher FJ 3rd. BAP1, a candidate tumor suppressor protein that interacts with BRCA1. Ann N Y Acad Sci. 1999;886:191–4.PubMedCrossRefPubMedCentralGoogle Scholar
  65. 65.
    Carbone M, Yang H, Pass HI, Krausz T, Testa JR, Gaudino G. BAP1 and cancer. Nat Rev Cancer. 2013;13(3):153–9.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Matatall KA, Agapova OA, Onken MD, Worley LA, Bowcock AM, Harbour JW. BAP1 deficiency causes loss of melanocytic cell identity in uveal melanoma. BMC Cancer. 2013;13:371.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Koopmans AE, Verdijk RM, Brouwer RW, van den Bosch TP, van den Berg MM, Vaarwater J, et al. Clinical significance of immunohistochemistry for detection of BAP1 mutations in uveal melanoma. Mod Pathol. 2014;27(10):1321–30.CrossRefGoogle Scholar
  68. 68.
    Kalirai H, Dodson A, Faqir S, Damato BE, Coupland SE. Lack of BAP1 protein expression in uveal melanoma is associated with increased metastatic risk and has utility in routine prognostic testing. Br J Cancer. 2014;111(7):1373–80.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Shah AA, Bourne TD, Murali R. BAP1 protein loss by immunohistochemistry: a potentially useful tool for prognostic prediction in patients with uveal melanoma. Pathology. 2013;45(7):651–6.PubMedCrossRefPubMedCentralGoogle Scholar
  70. 70.
    Szalai E, Wells JR, Ward L, Grossniklaus HE. Uveal melanoma nuclear BRCA1-associated protein-1 immunoreactivity is an indicator of metastasis. Ophthalmology. 2018;125(2):203–9.  https://doi.org/10.1016/j.ophtha.2017.07.018.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Griewank KG, van de Nes J, Schilling B, Moll I, Sucker A, Kakavand H, et al. Genetic and clinico-pathologic analysis of metastatic uveal melanoma. Mod Pathol. 2014;27(2):175–83.PubMedCrossRefPubMedCentralGoogle Scholar
  72. 72.
    McCarthy C, Kalirai H, Lake SL, Dodson A, Damato BE, Coupland SE. Insights into genetic alterations of liver metastases from uveal melanoma. Pigment Cell Melanoma Res. 2016;29(1):60–7.PubMedCrossRefPubMedCentralGoogle Scholar
  73. 73.
    Farquhar N, Thornton S, Coupland S, Coulson J, Sacco J, Krishna Y, et al. Patterns of BAP1 protein expression provide insights into prognostic significance and the biology of uveal melanoma. J Pathol Clin Res. 2017;4(1):26–38.PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Landreville S, Agapova OA, Matatall KA, Kneass ZT, Onken MD, Lee RS, et al. Histone deacetylase inhibitors induce growth arrest and differentiation in uveal melanoma. Clin Cancer Res. 2012;18(2):408–16.PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Abdel-Rahman MH, Pilarski R, Cebulla CM, Massengill JB, Christopher BN, Boru G, et al. Germline BAP1 mutation predisposes to uveal melanoma, lung adenocarcinoma, meningioma, and other cancers. J Med Genet. 2011;48(12):856–9.PubMedCrossRefPubMedCentralGoogle Scholar
  76. 76.
    Haugh AM, Njauw CN, Bubley JA, Verzi AE, Zhang B, Kudalkar E, et al. Genotypic and phenotypic features of BAP1 cancer syndrome: a report of 8 new families and review of cases in the literature. JAMA Dermatol. 2017;153(10):999–1006.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Testa JR, Cheung M, Pei J, Below JE, Tan Y, Sementino E, et al. Germline BAP1 mutations predispose to malignant mesothelioma. Nat Genet. 2011;43(10):1022–5.PubMedCentralCrossRefGoogle Scholar
  78. 78.
    Rai K, Pilarski R, Boru G, Rehman M, Saqr AH, Massengill JB, et al. Germline BAP1 alterations in familial uveal melanoma. Genes Chromosomes Cancer. 2017;56(2):168–74.PubMedCrossRefPubMedCentralGoogle Scholar
  79. 79.
    Pilarski R, Cebulla CM, Massengill JB, Rai K, Rich T, Strong L, et al. Expanding the clinical phenotype of hereditary BAP1 cancer predisposition syndrome, reporting three new cases. Genes Chromosomes Cancer. 2014;53(2):177–82.PubMedCrossRefPubMedCentralGoogle Scholar
  80. 80.
    Rai K, Pilarski R, Cebulla CM, Abdel-Rahman MH. Comprehensive review of BAP1 tumor predisposition syndrome with report of two new cases. Clin Genet. 2016;89(3):285–94.PubMedCrossRefPubMedCentralGoogle Scholar
  81. 81.
    Alsafadi S, Houy A, Battistella A, Popova T, Wassef M, Henry E, et al. Cancer-associated SF3B1 mutations affect alternative splicing by promoting alternative branchpoint usage. Nat Commun. 2016;7:10615.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    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(10):1122–9.PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Johnson CP, Kim IK, Esmaeli B, Amin-Mansour A, Treacy DJ, Carter SL, et al. Systematic genomic and translational efficiency studies of uveal melanoma. PLoS One. 2017;12(6):e0178189.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    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(4):4624–31.CrossRefPubMedGoogle Scholar
  85. 85.
    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(6):675–80.PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Ehlers JP, Worley L, Onken MD, Harbour JW. DDEF1 is located in an amplified region of chromosome 8q and is overexpressed in uveal melanoma. Clin Cancer Res. 2005;11(10):3609–13.PubMedCrossRefPubMedCentralGoogle Scholar
  87. 87.
    Laurent C, Valet F, Planque N, Silveri L, Maacha S, Anezo O, et al. High PTP4A3 phosphatase expression correlates with metastatic risk in uveal melanoma patients. Cancer Res. 2011;71(3):666–74.PubMedCrossRefPubMedCentralGoogle Scholar
  88. 88.
    Worley LA, Long MD, Onken MD, Harbour JW. Micro-RNAs associated with metastasis in uveal melanoma identified by multiplexed microarray profiling. Melanoma Res. 2008;18(3):184–90.PubMedCrossRefPubMedCentralGoogle Scholar
  89. 89.
    Radhakrishnan A, Badhrinarayanan N, Biswas J, Krishnakumar S. Analysis of chromosomal aberration (1, 3, and 8) and association of microRNAs in uveal melanoma. Mol Vis. 2009;15:2146–54.PubMedPubMedCentralGoogle Scholar
  90. 90.
    Ling JW, Lu PR, Zhang YB, Jiang S, Zhang ZC. miR-367 promotes uveal melanoma cell proliferation and migration by regulating PTEN. Genet Mol Res. 2017;16:3.  https://doi.org/10.4238/gmr16039067.CrossRefGoogle Scholar
  91. 91.
    Venkatesan N, Kanwar J, Deepa PR, Khetan V, Crowley TM, Raguraman R, et al. Clinico-pathological association of delineated miRNAs in uveal melanoma with monosomy 3/disomy 3 chromosomal aberrations. PLoS One. 2016;11(1):e0146128.PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Zhou J, Jiang J, Wang S, Xia X. Oncogenic role of microRNA20a in human uveal melanoma. Mol Med Rep. 2016;14(2):1560–6.PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Yan D, Zhou X, Chen X, Hu DN, Dong XD, Wang J, et al. MicroRNA-34a inhibits uveal melanoma cell proliferation and migration through downregulation of c-Met. Invest Ophthalmol Vis Sci. 2009;50(4):1559–65.PubMedCrossRefGoogle Scholar
  94. 94.
    Chen X, Wang J, Shen H, Lu J, Li C, Hu DN, et al. Epigenetics, microRNAs, and carcinogenesis: functional role of microRNA-137 in uveal melanoma. Invest Ophthalmol Vis Sci. 2011;52(3):1193–9.PubMedCrossRefGoogle Scholar
  95. 95.
    Ma YB, Song DW, Nie RH, Mu GY, Yoo JH, Shi DS, et al. MicroRNA-32 functions as a tumor suppressor and directly targets EZH2 in uveal melanoma. Genet Mol Res. 2016;15(2):889–904.Google Scholar
  96. 96.
    Lu L, Yu X, Zhang L, Ding X, Pan H, Wen X, et al. The long non-coding RNA RHPN1-AS1 promotes uveal melanoma progression. Int J Mol Sci. 2017;18(1):pii: E226.  https://doi.org/10.3390/ijms18010226.CrossRefGoogle Scholar
  97. 97.
    Maat W, van der Velden PA, Out-Luiting C, Plug M, Dirks-Mulder A, Jager MJ, et al. Epigenetic inactivation of RASSF1a in uveal melanoma. Invest Ophthalmol Vis Sci. 2007;48(2):486–90.PubMedCrossRefGoogle Scholar
  98. 98.
    Mobuchon L, Battistella A, Bardel C, Scelo G, Renoud A, Houy A, et al. A GWAS in uveal melanoma identifies risk polymorphisms in the CLPTM1L locus. NPJ Genom Med. 2017;2:pii: 5.  https://doi.org/10.1038/s41525-017-0008-5.CrossRefGoogle Scholar
  99. 99.
    Krishna Y, McCarthy C, Kalirai H, Coupland SE. Inflammatory cell infiltrates in advanced metastatic uveal melanoma. Hum Pathol. 2017;66:159–66.PubMedCrossRefGoogle Scholar
  100. 100.
    Singh AD, Tubbs R, Biscotti C, Schoenfield L, Trizzoi P. Chromosomal 3 and 8 status within hepatic metastasis of uveal melanoma. Arch Pathol Lab Med. 2009;133(8):1223–7.PubMedGoogle Scholar
  101. 101.
    Trolet J, Hupe P, Huon I, Lebigot I, Decraene C, Delattre O, et al. Genomic profiling and identification of high-risk uveal melanoma by array CGH analysis of primary tumors and liver metastases. Invest Ophthalmol Vis Sci. 2009;50(6):2572–80.PubMedCrossRefGoogle Scholar
  102. 102.
    Luscan A, Just PA, Briand A, Burin des Roziers C, Goussard P, Nitschke P, et al. Uveal melanoma hepatic metastases mutation spectrum analysis using targeted next-generation sequencing of 400 cancer genes. Br J Ophthalmol. 2015;99(4):437–9.PubMedCrossRefGoogle Scholar
  103. 103.
    Meir T, Dror R, Yu X, Qian J, Simon I, Pe’er J, et al. Molecular characteristics of liver metastases from uveal melanoma. Invest Ophthalmol Vis Sci. 2007;48(11):4890–6.PubMedCrossRefGoogle Scholar

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© Springer Nature Singapore Pte Ltd. 2020

Authors and Affiliations

  • Helen Kalirai
    • 1
  • Alexander Iu. Tsygankov
    • 2
  • Sophie Thornton
    • 1
  • Svetlana V. Saakyan
    • 2
    • 3
  • Sarah E. Coupland
    • 4
    Email author
  1. 1.Molecular and Clinical Cancer MedicineInstitute of Translational Medicine, University of LiverpoolLiverpoolUK
  2. 2.Department of Ocular Oncology and RadiologyMoscow Helmholtz Research Institute of Eye DiseasesMoscowRussian Federation
  3. 3.Department of Eye DiseasesMoscow Helmholtz Research Institute of Eye DiseasesMoscowRussian Federation
  4. 4.Molecular and Clinical Cancer MedicineRoyal Liverpool and Broadgreen University, Hospital NHS Trust, University of LiverpoolLiverpoolUK

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