Prognostic Factors in Uveal Melanoma

Uveal melanoma is the most common intra-ocular tumour in the western world with an annual incidence of seven per million. Approximately 50% of the patients treated by enucleation dye eventually due to metastatic disease. Besides enucleation there are nowadays more conservative treatment methods aimed at sparing the affected eye and retaining vision, s.a. transpupillary thermotherapy (TTT), plaque radiotherapy, proton beam or stereotactic radiotherapy. The effect of radiotherapy in uveal melanoma cell lines and primary uveal melanoma was described in the first part of this thesis. The second part of this thesis focuses on identification of clinical and genetic prognostic parameters. It concentrates on parameters that identify patients at high risk of metastatic disease, in particular. Several prognostic markers have been associated with disease free survival. We describe the analysis of 120 uveal melanomas of patients treated with enucleation for chromosomal! changes using conventional cytogenetics, FISH and CGH techniques. Concurrent loss of chromosome region 1p and monosomy of chromosome 3 was the strongest predictor for disease free survival of uveal melanoma patients. The last part focuses on delineation of critical regions and genes of interest. Besides monosomy 3 some tumours may show partial loss of chromosome 3. Two regions, one on the p-arm and one on the q-arm, might be involved in metastases. We studied the partial aberrations observed in uveal melanoma cell lines. A region on chromosome 3q was delineated and reduced the size of the smallest region of overlap compared with literature. The strong correlation between concurrent loss of chromosome region 1p36 and monosomy 3 was suggestive for genes encoded on these chromosomes that might play a role in tumour progression. Two genes, p73 and p63, located on chromosome 3q24 and 1p36 respectively were investigated. Furthermore, we describe mutation analysis of BRAF in thirty-three primary uveal melanoma and commonly used uveal melanoma cell lines.

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