Scientific and clinical implications of heterogeneity in uveal melanoma

Lange, M.J. de (2024)

Doctoral Thesis

Uveal melanoma, as opposed to cutaneous melanoma, is a tumor which is predominantly located in the center of the eye. Given its potential aggressive nature with fatal consequences, it is important to start treatment in a timely manner. Currently, treatment consists of decreasing the size of the tumor by means of radiation therapy or surgery, but by mapping the genetic makeup of uveal melanoma, personalized treatment potentially becomes possible. In this thesis we tried to solve a piece of this genetic puzzle by focusing on genetic and cellular differences within and between different uveal melanoma. By means of an innovative new technique, digital PCR, we aimed to visualize this so-called heterogeneity. We demonstrate that we can accurately assess which genetic aberrations are present in uveal melanoma. Moreover, we show in what percentage of cells these aberrations are present. Additionally, we illustrate which cell types play an important role in uveal melanoma development. This way, we characterized a substantial amount of different uveal melanoma based on their heterogeneity profile. Lastly, we display whether and how uveal melanomas with a specific heterogeneity profile are susceptible to treatment.

• Uveal Melanoma
• Genetic heterogeneity
• Cellular heterogeneity
• Digital PCR
• Mutation signatures
• Immune infiltrate

• All authors: Lange, M.J. de
• Supervisor: Luyten, G.P.M.; Jager, M.I.
• Co-supervisor: Velden, P.A. van der
• Committee: Boon, C.J.F.; Maier, A.B.; Langerak, A.W.; Vu, T.H.K.; Gruis, N.A.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2024-06-13
• ISBN (print): 9789493330894
• Sponsorship: Dutch Cancer Society (KWF), grant registration code UL 2011-4991