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Genetic prognostication in uveal melanoma
Uveal melanoma (UM) is an aggressive intraocular tumor with a high propensity to metastasize. Accurate prognostication is relevant for patient counselling, planning of follow-up and stratification of patients in clinical trials. Discoveries of prognostically relevant genetic markers in the last few decades have fuelled the advancement of prognostication in UM considerably. In this thesis, we explored ways of improving genetic prognostication in UM,
evaluated the effect of irradiation on chromosome testing, and investigated the
association of DNA repair genes and epigenetic regulators with prognosis. We reveal that chromosome markers of high malignancy such as monosomy 3 and chromosome 8q gain are less often observed in patients who die due to metastases at a late stage. We demonstrate that combining the AJCC staging and chromosome 3 and 8q status results in enhanced risk stratification. We provide evidence that...
Uveal melanoma (UM) is an aggressive intraocular tumor with a high propensity to metastasize. Accurate prognostication is relevant for patient counselling, planning of follow-up and stratification of patients in clinical trials. Discoveries of prognostically relevant genetic markers in the last few decades have fuelled the advancement of prognostication in UM considerably. In this thesis, we explored ways of improving genetic prognostication in UM,
evaluated the effect of irradiation on chromosome testing, and investigated the
association of DNA repair genes and epigenetic regulators with prognosis. We reveal that chromosome markers of high malignancy such as monosomy 3 and chromosome 8q gain are less often observed in patients who die due to metastases at a late stage. We demonstrate that combining the AJCC staging and chromosome 3 and 8q status results in enhanced risk stratification. We provide evidence that supports the taking of biopsies before radiotherapy is applied since chromosome testing seems to fail more often in irradiated tumors. Furthermore, we show that evaluating the role of DNA repair and epigenetics in uveal melanoma can help in unraveling the biology of uveal melanoma and identifying new markers for prognostication.
- All authors
- Dogrusoz, M.
- Supervisor
- Jager, M.J.; Luyten, G.P.M.
- Committee
- Kiilgaard, J.F.; Killic, E.; Asperen, C.J. van
- Qualification
- Doctor (dr.)
- Awarding Institution
- Medicine, Leiden University Medical Center (LUMC) , Leiden University
- Date
- 2018-04-17
- ISBN (print)
- 9789462999459
Funding
- Sponsorship
- - Horizon 2020 UM CURE (European Union) - The Eye Cancer Network (New York, NY, United States of America - Stichting Blinden-Penning (Amsterdam, The Netherlands)