Leiden University Scholarly Publications

Persistent URL of this record https://hdl.handle.net/1887/61625

In Collections

This item can be found in the following collections:

Dogrusoz, M. (2018)

Genetic prognostication in uveal melanoma

Doctoral Thesis

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...

Show more

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.

Show less
Uveal melanoma
Ocular melanoma
Choroidal melanoma
Survival
Prognosis
Prognostication
Genetic
Genetic test
Genes
Chromosomes
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)