Clinical applications of DNA methylation in gastrointestinal cancer
Maat, M.F.G. de
Citation
Maat, M. F. G. de. (2010, May 12). Clinical applications of DNA methylation in gastrointestinal cancer. Retrieved from https://hdl.handle.net/1887/15373
Version: Corrected Publisher’s Version
License: Licence agreement concerning inclusion of doctoral thesis in the Institutional Repository of the University of Leiden
Downloaded from: https://hdl.handle.net/1887/15373
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Clinical applications of DNA methylation in gastrointestinal cancer
Proefschrift
ter verkrijging van de graad van Doctor aan de Universiteit Leiden, op gezag van Rector Magnificus Prof. mr. P.F. van der Heijden,
volgens het besluit van het College voor Promoties te verdedigen op woensdag 12 mei 2010
klokke 16.15 uur
door Michiel Frank Gerard de Maat geboren te Baexem in 1979.
Promotiecommissie:
Promotores:
Prof. dr. C.J.H. van de Velde Prof. dr. R.A.E.M. Tollenaar Copromotor:
D.S.B. Hoon, PhD (John Wayne Cancer Institute, Santa Monica, USA) Overige leden:
Prof. dr. J. Morreau
Prof. dr. I.H. Borel Rinkes (Utrecht University Medical Center) Prof. dr. J.H.J.M. van Krieken (University Medical Center Nijmegen) Prof. dr. G.A. Meijer (Vrije Universiteit Medical Center, Amsterdam) Dr. P.J.K. Kuppen
“Hoe ver je gaat heeft met afstand niets te maken, hooguit met de tijd.
Hoe diep je gaat heeft met denken niets te maken, hooguit met een wil.
Hoe recht je staat heeft met zwaarte niets te maken, hooguit met de wind.”
vrij naar: omarm me, Bløf
Aan mijn ouders, Voor Debbie.
Cover:
Digital impressionistic collage of sodium metabisulfite cristal formation in aeqeous solution.
Treatment of DNA with sodium metabisulfite is the key step to detect whether DNA is methylated.
ISBN nr: 978-90-8590-044-3 Copyright M.F.G. de Maat, 2010
Colofon:
Cover design and thesis layout by DL graphics, Kerkrade, the Netherlands www.dlgraphics.nl
Printed by Schrijen-Lippertz, Voerendaal, the Netherlands
The research described in this thesis and the printing was financially supported by grants from: Ruth and Martin H. Weil Fund, the Rod Fasone Memorial Fund, the Gonda Foundation, Coates Laboratories at JWCI, the Drie Lichten Foundation, Novartis Oncology, Eurotec BV
CONTENTS
•
General Introduction•
Outline of Thesis•
Section 1: Technical Advancements CHAPTER 1°
Synthesis of universal unmethylated control DNA by nested whole genome amplification with Φ29 DNA polymeraseBiochem Biophys Res Commun. 2005 Apr 1;329(1):219-23 CHAPTER 2
°
Methylation of p16 and Ras Association Domain Family Protein 1a during Colorectal Malignant TransformationMol Cancer Res. 2006 May;4(5):303-9 CHAPTER 3
°
Assessment of Methylation Events during Colorectal Tumor Progression by Absolute Quantitative Analysis of Methylated AllelesMol Cancer Res. 2007 May;5(5):461-71 CHAPTER 4
°
LINE-1 methylation analysis in colorectal cancer shows progression of hypo- methylation at early stageSubmitted for Publication
•
Section 2: DNA methylation in gastrointestinal adenocarcinoma CHAPTER 5°
Epigenetic Silencing of Cyclooxygenase-2 Affects Clinical Outcome in Gastric CancerJ Clin Oncol. 2007 Nov 1;25(31):4887-94 CHAPTER 6
°
Quantitative Analysis of Methylation of Genomic Loci in Early-Stage Rectal Cancer Predicts Distant RecurrenceJ Clin Oncol. 2008 May 10;26(14):2327-35 CHAPTER 7
°
Identification of a Quantitative MINT Locus Methylation Profile Predicting Local Regional Recurrence of Rectal CancerAccepted for publication in Clinical Cancer Research
5 Contents
9 29 35
37
49
65
85
99
101
121
143
CHAPTER 8
°
Development of Sporadic Microsatellite Instability in Colorectal Tumors Requires Hypermethylation at Methylated-IN-Tumor loci in AdenomaSubmitted for publication
•
General discussion and future perspectives•
English summary•
Nederlandse samenvatting•
Acknowledgements•
Curriculum Vitae•
List of Publications•
Color Figures6 Contents
163
185 199 207 215 217 219 221
7 Contents
8
