Genetics of Uveal Melanoma

Uveal melanoma is the most common type of primary eye cancer in adults, affecting 0.7/100,000 of the Western population yearly (Egan et al., 1988). The melanoma originates from neural crest derived melanocytes of the uvea (choroid, ciliary body and iris) and despite enucleation or conservative treatment half of patients die of, most often late appearing, metastatic disease (15-year survival: 53%) (Diener-West et al., 1992; Gamel et al., 1993; Kujala et al., 2003). To detect these (micro) metastasising cells in an early phase is one of the main challenges in the (uveal melanoma) oncology field and a prerequisite for proper patient selection in future therapeutic interventions. Several clinical, histological and genetic markers have been identified to predict poor prognosis in uveal melanoma patients. Genetic markers as chromosome 3 loss or the expression of a specific set of genes have proven to be far out the most significant prognostic markers. This will not only facilitate diagnosis and prediction of prognosis but will also assist in selecting patients for adjuvant therapy and the monitoring of circulating tumour cells. Alternatively, some of the tumour markers as GNAQ/GNA11, or BAP1 may serve as targets for new types of intervention tackling that specific pathway. In this chapter, the most recent cytogenetic and molecular genetic approaches will be discussed along with the most important findings and their value for current and future management of patients with uveal melanoma.