Unravelling vascular tumors : combining molecular and computational biology

IJzendoorn, D.G.P. van (2020)

Doctoral Thesis

This thesis contributes to understanding vascular tumors and other soft-tissue sarcomas. For epithelioid hemangioma a new translocation is described leading to truncation of the FOS protein. It was found that this truncation leads to a longer half-life of the FOS protein, which could explain the tumorigenesis of epithelioid hemangioma. For patients with pseudomyogenic hemangioendothelioma the mechanism of action for treatment with telatinib is elucidated. For pseudomyogenic hemangioendothelioma a new cell-line based model was developed. With CRISPR/Cas9 the characterizing translocation could be inserted into the DNA of endothelial cells, thereby recapitulating multiple characteristics of pseudomyogenic hemangioendothelioma. Throughout this thesis computational biology was used to study vascular tumors and other soft-tissue sarcomas to gain new insights and find potential new treatment options.

• Vascular tumor
• Soft-tissue sarcoma
• Epithelioid hemangioma
• Pseudomyogenic hemangioendothelioma
• CRISPR Cas9

• All authors: IJzendoorn, D.G.P. van
• Supervisor: Bovée, J.V.M.G.
• Co-supervisor: Szuhai, K.
• Committee: Tanke, H.J.; Graaf, W.T.A. van der; Kuijer, M.L.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2020-01-16
• ISBN (print): 9789083037615