Genetic Abnormalities in Uveal Melanoma

Melanocytic tumours are believed to arise from the neural crest-derived melanocytes. Five to twelve percent of all melanomas are located in the eye, making it, after the skin, the second most common site of melanomas (Egan et al., 1988; Chang et al., 1998). Uveal melanoma is the most common form of primary eye cancer in adults, affecting approximately 7 per million people in the Western world each year (Egan et aI., 1988). In persons over 20 years of age, melanoma is the reported diagnosis in 80% of all primary intraocular cancers. Most uveal melanomas are located in the ciliary body and/or the choroid (23% and 72%, respectively), whereas iris melanomas account for only a small percentage of these tnmours (5%) (Yanoff and Fine, 1989). The majority of iris melanomas consist of non-metastasising lesions and 'Will not be discussed in this thesis. Although less than 2% of uveal melanoma patients have clinically detectable metastases at presentation, 50% of all patients ultimately die of metastases, predominantly located in the liver. The median survival time after discovery of the primary tumour is 6.5 years (McLean, 1993), and peaks between the second and the fourth year (Zimmerman et aI., 1978). The 5, 10 and 15 year survival rates based on tumour related mortality are 72%, 59% and 53% respectively (Gamel et aI., 1993; McLean and Gamel, 1998). As of yet, no effective treatment is available once metastatic disease has developed and the survival time after its diagnosis is limited to two to seven months (Seddon et aI., 1983; Kath et aI., 1993).