Cover Page
The handle http://hdl.handle.net/1887/82754 holds various files of this Leiden University dissertation.
Author: IJzendoorn, D.G.P. van
Unravelling Vascular Tumors:
Combining Molecular and
Publication of this thesis was financially supported by the Department of Pathology, Leiden University Medical Center.
Cover art: Pollock, J. (ca. 1938-41) Untitled [brush and India ink on cardboard]
© 2019. Image copyright The Metropolitan Museum of Art/Art Resource/Scala, Florence.
Printed by: Print Service, Ede, the Netherlands.
Thesis layout: based on a template by Marieke Kuijjer (https://github.com/mararie/thesis).
Unravelling Vascular Tumors:
Combining Molecular and
Computational Biology
Proefschrift
ter verkrijging van
de graad van Doctor aan de Universiteit Leiden,
op gezag van Rector Magnificus prof.mr. C.J.J.M. Stolker,
volgens besluit van het College voor Promoties
te verdedigen op donderdag 16 januari 2020
klokke 15.00 uur
door
David Gerardus Pieter van IJzendoorn
geboren te Leiden
Promotor: Prof. dr. J.V.M.G. Bovée Co-promotor: Dr. K. Szuhai
Leden promotiecommissie: Prof. dr. H.J. Tanke
Prof. dr. W.T.A. van der Graaf (Netherlands Cancer Institute, Amsterdam)
Contents
1 General introduction 9
2 Vascular tumors of bone: the evolvement of a classification based on
molecular developments 25
I
Diagnosis and treatment
51
3 Fusion events lead to truncation of FOS in epithelioid hemangioma of
bone 53
4 Telatinib is an effective targeted therapy for pseudomyogenic
heman-gioendothelioma 69
II
Model systems
91
5 Functional analyses of a human vascular tumor FOS variant identify a novel degradation mechanism and a link to tumorigenesis 93 6 Pseudomyogenic hemangioendothelioma recapitulated in endothelial cells
from human induced pluripotent stem cells engineered to express the
SERPINE1-FOSB translocation 111
III
Computational biology
145
7 PyPanda: a Python package for gene regulatory network reconstruction147 8 Gene regulatory network analysis of translocation driven vascular
tu-mors 153
9 Machine learning analysis of gene expression data reveals novel diag-nostic and progdiag-nostic biomarkers and identifies therapeutic targets for
soft tissue sarcomas 167
IV
Summary and discussion
191
10 Summary and discussion 193
11 Nederlandse samenvatting 203
V
Appendices
209
Curriculum vitae 211
List of publications 213
