Transcript genetic characterization of chemotherapy response in ovarian cancer

(Epi)genetic characterization of chemotherapy
response in ovarian cancer:
Finding better markers, models and targets for therapy
Tushar Tomar
Thesis printing was financially supported by
University Medical Center Groningen
University of Groningen
CrownBio
MDx Health
BioDiscovery Inc
ChipSoft
Innovative Research of America
Axon MedChem
and
Stichting Werkgroep Interne Oncologie
Graduate School of Medical Science
The research presented in this thesis was financially supported by
KWF kankerbestrijding (RUG 4833-2010, RUG 5231-2011 en RUG 5477-2012), Jan Kornelis de Cock
stichting and the ‘Kleine vis-grote vis’ Stimuleringsfonds Research Obstetrie & Gynaecologie, UMCG
Cover design
Tushar Tomar and Pharma Pulse
Printing
CPI Koninklijke wöhrmann B.V., Zutphen, The Netherlands
Layout
Pharma Pulse (www.pharmapulse.net)
Dissertation of University of Groningen, Groningen, The Netherlands
ISBN: 978-90-367-9134-2 (printed)
ISBN: 978-90-367-9135-9 (digital)
© Tushar Tomar, Groningen, 2016
email ID: [email protected]
All rights reserved. No parts of this thesis may be reproduced or transmitted in any form or by any means,
without written permission from the author.
(Epi)genetic characterization of chemotherapy
response in ovarian cancer:
Finding better markers, models and targets for therapy
PhD thesis
to obtain the degree of PhD at the
University of Groningen
on the authority of the
Rector Magnificus Prof. E. Sterken
and in accordance with
the decision by the College of Deans.
This thesis will be defended in public on
Monday 10 October 2016 at 12.45 hours
by
Tushar Tomar
born on 28 October 1987
in Jalandhar, India
Supervisors
Prof. dr. S. de Jong
Prof. dr. A.G.J. van der Zee
Co-supervisor
Dr. G.B.A. Wisman
Assessment committee
Prof. dr. E.M.J.J. Berns
Prof. dr. H.J.M Groen
Prof. dr. J.J. Schuringa
Dedicated to My Parents and Beloved Wife
Paranymphs
Gert Jan Meersma
Shivashankar Khanapur
Contents
Chapter 1
General introduction to the thesis
Chapter 2
Genome-wide integrated epigenomics analysis identifies
FZD10 for platinum sensitivity in ovarian cancer
23
Chapter 3
Checkpoint Kinase 2 (Chk2) supports sensitivity to
platinum-based treatment in high-grade serous ovarian
cancer
49
Chapter 4
Biobanking of patient and patient-derived xenograft (PDX)
varian tumour tissue: efficient preservation with low and
high FCS based methods
65
Chapter 5
Genome-wide methylation profiling of ovarian cancer
patient-derived xenograft (PDXs) treated with the
demethylating agent decitabine identifies novel
epigenetically regulated genes and pathways
91
Chapter 6
Dual wavelength near-infrared fluorescence imaging
of VEGF and IGF-1R in ovarian cancer patient-derived
xenografts
117
Chapter 7
Functional genomic mRNA profiling identifies novel
platinum chemoresponse-associated genes in high grade
serous ovarian cancer
145
Chapter 8
Summary, discussion and future Perspectives
165
Chapter 9
Nederlandse Samenvatting
175
Appendices
Curriculum Vitae
184
List of Publications
188
List of Abbreviations
190
Acknowledgements
193
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