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Unpacking the genetic etiology of uveal melanoma

ABSTRACT Introduction Uveal melanoma (UM) is the most common primary intraocular tumor affecting adults. ~50% of patients will develop metastatic disease, mainly in the liver, for which there is currently no standard of care. The multi-faceted genetic etiology of UM informs prognosis and advises the clinical management of patients. Areas covered This review highlights the multifarious nature of the genetics that differentiate uveal nevi from UM, that initiate tumorigenesis and ultimately drive metastasis, and how these can be incorporated to multivariate models to predict whether and approximately when the metastatic disease will occur. Expert opinion Despite not being able to utilize current genomic biomarkers as therapeutically actionable targets in UM at present, advances in our understanding of this cancer, may lead to their inclusion to predict response to emerging therapies. Prognostication for individual patients is likely to progress from binary classifications of high- and low-metastatic risk, utilizing a multi-factorial approach to design molecular assays. Improvement in our comprehension of the genetic etiology of UM will bring us closer to the development of effective treatments.