PhD defence J.Q.N. (Josephine) Nguyen

Below is a brief summary of the dissertation: 

Uveal melanoma (UM) is a rare but aggressive eye cancer that often spreads to other organs. This thesis provides new insights into the biology of the disease, highlights possible treatment options, and lays the groundwork for better laboratory models. A key finding is the role of mistakes in RNA splicing, a process essential for normal cell function. Mutations in the splicing gene SF3B1 were shown to drive disease in different ways, some patients develop metastases early, while others remain disease-free for many years. Differences in gene activity between these groups may help predict outcomes. In this thesis, a study also tested the experimental drug E7107, which blocks aberrant splicing. It was found to trigger cancer cell death in tumors with SF3B1 mutations, suggesting that such treatments may hold promise, especially in combination with other drugs. In addition, articles in this thesis identified several genetic markers, including changes in chromosome 8q and genes like FOXD1 and RBFOX2, which are linked to aggressive disease and poor survival. Finally, progress has been made in developing a laboratory model of UM using advanced gene-editing techniques. Such models are essential to study how the cancer evolves and to test new therapies. Together, the findings of this thesis offer valuable knowledge that brings science closer to more effective treatments for patients with this challenging disease.