University of Groningen
On the origins of pediatric brain cancer
Bockaj, Irena
DOI:
10.33612/diss.156023051
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Publication date:
2021
Link to publication in University of Groningen/UMCG research database
Citation for published version (APA):
Bockaj, I. (2021). On the origins of pediatric brain cancer: Exploring the role of genome instability in
development and disease. University of Groningen. https://doi.org/10.33612/diss.156023051
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On the origins of pediatric brain cancer
Exploring the role of genome instability
in development and disease
The work described in this thesis was conducted at the Departments of Pediatric Oncology and Hematology/Pediatrics and the European Research Institute for the Biology of Ageing (ERIBA), University Medical Centre Groningen, University of Groningen, the Netherlands.
Cover design & Layout: Irena Bočkaj Printing: Gildeprint B.V., www.gildeprint.nl
Copyright © Irena Bočkaj, Groningen, The Netherlands. All rights reserved. No part of this book may be reproduced or transmitted, in any form or by any means without prior permission of the author.
On the origins
of pediatric brain cancer
Exploring the role of genome instability in development and disease
PhD thesis
to obtain the degree of PhD at the University of Groningen
on the authority of the Rector Magnificus Prof. C. Wijmenga
and in accordance with the decision by the College of Deans. This thesis will be defended in public on Monday 15 February 2021 at 11.00 hours
by
Irena Bočkaj
born on 19 September 1988 in Mostar, Bosnia & HerzegovinaSupervisor
Prof. E.S.J.M. de BontCo-supervisor
Dr. S.W.M. Bruggeman
Assessment Committee
Prof. H.J.P. te Riele Prof. B.J.L. Eggen Prof. M.A.T.M. van Vugt
Table of Contents
Chapter 1
General Introduction: Pediatric Brain Cancers & Brain Development
On the origins of pediatric brain cancer: when normal development goes astray.
6
Scope of this thesis
31Chapter 2
The Developing Brain & Genome Instability
Vulnerability to aneuploidy in the developing brain: a path to cancer?
40
Chapter 3
Pediatric Medulloblastoma & Cell-of-origin
The developmental stage of the medulloblastoma cell-of-origin is maintained in cancer and restricts Hedgehog pathway usage and drug sensitivity.
60
Chapter 4
Pediatric Medulloblastoma & Genome Instability
A role for genomic instability in pediatric medulloblastoma: modelling medulloblastoma using CIN as a driver.
103
Chapter 5
Pediatric high-grade glioma & Cell-of-origin
In quest of the pontine glioma cell-of-origin.
134
Chapter 6
Pediatric High-Grade Glioma & Genome Instability
The H3.3K27M oncohistone affects replication stress outcome and provokes genomic instability in pediatric glioma.
160
Chapter 7
General discussion & Conclusion
194Appendices
Revisiting the chromosome segregation checkpoint (Bioessays 2017) 218
List of abbreviations 220
Dutch summary 222
Acknowledgements 226
