A review of prognostic biomarkers in uveal melanomas

Akriti Kashyap, Preeti Tripathi, Arijit Sen


Prognostication of uveal melanomas (UM) has evolved from basic histopathological factors like tumour size, location and cell morphology to more sophisticated methods like counting chromosomal gains and losses which can be detected using FISH analysis and karyotyping. A number of driver mutations have been discovered which allow testing of response to targeted therapies. GNAQ and GNA11 mutations are early events while BAP1, SF3B1 and EIF1AX mutations occur later. Gene expression profiling is a highly accurate and informative standard for molecular prognostication. In addition, since UM spreads hematogenously, therefore, blood biomarkers may be helpful for monitoring the disease progression. Thus, understanding the prognostic significance of these mutations and blood biomarkers could facilitate their use in precision medicine


Biomarkers, Melanomas, Prognostication, Uveal

Full Text:



McLaughlin CC, Wu XC, Jemal A, Martin HJ, Roche LM, Chen VW. Incidence of non-cutaneous melanomas in the US. Cancer. 2005;103:1000-7.

Finger PT. 7th Edition, AJCC-UICC ophthalmic oncology task force. The 7th edition AJCC staging system for eye cancer: an international language for ophthalmic oncology. Arch Pathol Lab Med. 2009;133:1197-8.

Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SA, Behjati S, Biankin AV, et al. Signatures of mutational processes in human cancer. Nature. 2013;500:415-21.

Hayward NK, Wilmott JS, Waddell N, Johansson PA, Field MA, Nones K, et al. Whole-genome landscapes of major melanoma subtypes. Nature. 2017;545:175-80.

Akbani R, Akdemir KC, Aksoy BA, Albert M, Ally A, Amin SB, et al. Genomic classification of cutaneous melanoma. Cell. 2015;161(7):1681-96.

Field MG, Harbour JW. Recent developments in prognostic and predictive testing in uveal melanoma. Curr Opin Ophthalmol. 2014;25(3):234-9.

Ambrosini G, Musi E, Ho AL, de Stanchina E, Schwartz GK. Inhibition of mutant GNAQ signaling in uveal melanoma induces AMPK-dependent autophagic cell death. Mol Cancer Ther. 2013;12:768-76.

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

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.

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.

Brantley M, Harbour JW. Deregulation of the Rb and p53 pathways in uveal melanoma. Am J Pathol. 2000;157:1795-801.

Mouriaux, Kherrouche Z, Maurage, Demailly, Labalette P, Saule S. Expression of the c-kit receptor in choroidal melanomas. Melanoma Res. 2003;13:161-6.

Park J, Diefenbach R, Joshua A, Kefford R, Carlino M. Oncogenic signalling in uveal melanoma. Pigment Cell Melanoma Res. 2018;31(6):661-72.

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(2):182-7.

Ling JW, Lu PR, Zhang YB, Jiang S, Zhang ZC. miR-367 promotes uveal melanoma cell proliferation and migration by regulating PTEN. Genet Molecular Res. 2017;16:120-6.

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;48:856-9.

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;99:1190-8.

Prescher G, Bornfeld N, Hirche H. Prognostic implications ofmonosomy 3 in uveal melanoma. Lancet. 1996;347:1222-5.

Dogrusoz M, Bagger M, Van Duinen SG, Kroes WG, Ruivenkamp CA, Böhringer 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;58:833-42.

Worley LA, Onken MD, Person E, Robirds D, Branson J, Char DH, et al. Transcriptomic versus chromosomal prognostic markers and clinical outcome in uveal melanoma. Clin Cancer Res. 2007;13:1466-71.

Tschentscher F, Husing J, Holter T, Kruse E, Dresen IG, Jöckel 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;63:2578-84.

Onken MD, Worley LA, Char DH, Augsburger JJ, Correa ZM, Nudleman E, et al. Collaborative ocular oncology group report no. 1: prospective validation of a multi-gene prognostic assay in uveal melanoma. Ophthalmol. 2012;119(8):1596-603.

Cochran AJ, Holland GN, Saxton RE, Damato BE, Foulds WR, Herschman HR, et al. Detection and quantification of S-100 protein in ocular tissues and fluids from patients with intraocular melanoma. Br J Ophthalmol. 1988;72(11):874-9.

Missotten GS, Tang NE, Korse CM. Prognostic value of S-100-beta serum concentration in patients with uveal melanoma. Arch Ophthalmol. 2003;121(8):1117-9.

Rodríguez, Marta B, Baameiro NL, Santiago-Varela M, Rodríguez P. Blood biomarkers of uveal melanoma: current perspectives. Clin Ophthalmol. 2020;14:157-69.

Schaller UC, Bosserhoff AK, Neubauer AS, Buettner R, Kampik A, Mueller AJ. Melanoma inhibitory activity: a novel serum marker for uveal melanoma. Melanoma Res. 2002;12(6):593-9.

Kadkol SS, Lin AY, Barak V, Kalickman I, Leach L, Valyi-Nagy K, et al. Osteopontin expression and serum levels in metastatic uveal melanoma: a pilot study. Invest Ophthalmol Vis Sci. 2006;47(3):802-6.