DNA Methylation: Approaches, Methods, and Applications

215 Pages·2004·9.422 MB·English

by  Esteller, Manel

DNA METHYLATION
Approaches, Methods,
and Applications
EDITED BY
Manel Esteller
CRC PR ESS
Boca Raton London New York Washington, D.C.
© 2005 by CRC Press LLC
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Library of Congress Cataloging-in-Publication Data
DNA methylation: approaches, methods and applications / edited by Manel Esteller.
p. cm.
Includes bibliographical references and index.
ISBN 0-8493-2050-X (alk. paper)
1. DNA--Methylation--Handbooks, manuals, etc. I. Esteller, Manel. II. Title.
QP624.5.M46D626 2004
616′.042—dc22 2004049665

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Preface
A quick glance at the number of references to DNA methylation in the searchable
biomedical databases, such as PubMed and others, or the frequency with which these
words appear on Internet websites and public databases demonstrates the current
boom in interest in DNA methylation. This book is born of the necessity to serve
that interest: it aims to be a comprehensive handbook covering the areas in which
DNA methylation is important, addressing how this modification may be studied for
academic and clinicopathological purposes and how it may be applied in therapeutic
strategies. Until now, the field has lacked this type of organized bibliographical
source, but this current book, with contributions from many of the leading experts
in the field of DNA methylation, makes good this absence.
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Editor
Manel Esteller graduated with honors in medicine from the University of Barcelona,
Catalonia, Spain, and then earned his Ph.D. cum laude from the University of
Barcelona. Dr. Esteller’s credits include the following: invited researcher at the
School of Biological and Medical Sciences, University of St. Andrews, Scotland,
and postdoctoral researcher and research associate at The Johns Hopkins University
and School of Medicine, Baltimore, Maryland. He is currently director of the Cancer
Epigenetics Branch at the Spanish National Cancer Centre (CNIO) in Madrid.
Through his efforts, the hypermethylation-associated silencing of tumor suppressor
genes is in the forefront not only of epigenetics, but also current cancer research.
The author of more than ninety original peer-reviewed manuscripts in biomedical
sciences, Dr. Esteller is a member of eight international scientific societies. He has
served as a reviewer for many journals and funding agencies in the biomedical area.
His numerous awards include Best Young Investigator, awarded by the European
Association for Cancer Research (2000), Best Young Cancer Researcher, awarded
by the European School of Medical Oncology (1999), and First Prize in Basic
Research at the Johns Hopkins Oncology Center (1999).
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Contributors
Esteban Ballestar Joseph F. Costello
Cancer Epigenetics Laboratory Department of Neurological Surgery
Spanish National Cancer Centre and The Brain Tumor Research Center
Madrid, Spain University of California
San Francisco, California
Robert Brown
Department of Medical Oncology Maurizio D’Esposito
Cancer Research UK, Beatson Institute of Genetics and Biophysics
Laboratories “Adriano Buzzati Traverso”
Glasgow University Consiglio Nazionale delle Ricerche
Glasgow, Scotland Naples, Italy
Michael W.-Y. Chan Jesus Espada
Department of Molecular Virology, Cancer Epigenetics Laboratory
Immunology, and Medical Genetics Spanish National Cancer Centre
Comprehensive Cancer Center Madrid, Spain
The Ohio State University
Columbus, Ohio Manel Esteller
Cancer Epigenetics Laboratory
Jonathan C. Cheng Spanish National Cancer Centre
Department of Urology Madrid, Spain
University of Southern
California/Norris Comprehensive Mario F. Fraga
Cancer Center Cancer Epigenetics Laboratory
Keck School of Medicine Spanish National Cancer Centre
Los Angeles, California Madrid, Spain
Susan J. Clark Jordi Frigola
Sydney Cancer Centre Institut de Recerca Oncologica
Kanematsu Laboratories Hospital Duran i Reynals
Royal Prince Alfred Hospital L’Hospitalet
Camperdown, Australia Barcelona, Spain
Rainer Claus Jens Hasskarl
Department of Hematology Department of Hematology
University of Freiburg Medical Center University of Freiburg Medical Center
Freiburg, Germany Freiburg, Germany
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Rui Henrique Maria Rosaria Matarazzo
Department of Otolaryngology — Institute of Genetics and Biophysics
Head and Neck Surgery “Adriano Buzzati Traverso”
The Johns Hopkins School of Medicine Consiglio Nazionale delle Ricerche
Baltimore, Maryland Naples, Italy
James G. Herman Maria F. Paz
The Sidney Kimmel Comprehensive Cancer Epigenetics Laboratory
Cancer Center Spanish National Cancer Centre
Johns Hopkins School of Medicine Madrid, Spain
Baltimore, Maryland
Miguel A. Peinado
Tim H.-M. Huang Institut de Recerca Oncologica
Department of Molecular Virology, Hospital Duran i Reynals
Immunology, and Medical Genetics L’Hospitalet
Comprehensive Cancer Center Barcelona, Spain
The Ohio State University
Columbus, Ohio Christoph Plass
Division of Human Cancer Genetics
Carmen Jerónimo Medical Research Facility
Department of Otolaryngology — The Ohio State University
Head and Neck Surgery Columbus, Ohio
The Johns Hopkins School of Medicine
Baltimore, Maryland Laura J. Rush
Department of Veterinary Biosciences
Peter A. Jones The Ohio State University
Department of Urology Columbus, Ohio
University of Southern
California/Norris Comprehensive Masahiko Shiraishi
Cancer Center Department of Molecular Virology,
Keck School of Medicine Immunology, and Medical Genetics
Los Angeles, California Comprehensive Cancer Center
The Ohio State University
Peter W. Laird Columbus, Ohio
Departments of Surgery and of
Biochemistry and Molecular Biology David Sidransky
University of Southern Department of Otolaryngology —
California/Norris Comprehensive Head and Neck Surgery
Cancer Center The Johns Hopkins School of Medicine
Los Angeles, California Baltimore, Maryland
Michael Lübbert Dominic J. Smiraglia
Department of Hematology Department of Cancer Genetics
University of Freiburg Medical Center Roswell Park Cancer Institute
Freiburg, Germany Buffalo, New York
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Nicole M. Sodir Daniel J. Weisenberger
Departments of Surgery and of Department of Urology
Biochemistry and Molecular Biology University of Southern
University of Southern California/Norris Comprehensive
California/Norris Comprehensive Cancer Center
Cancer Center Keck School of Medicine
Los Angeles, California Los Angeles, California
Maria Strazzullo
Institute of Genetics and Biophysics
“Adriano Buzzati Traverso”
Consiglio Nazionale delle Ricerche
Naples, Italy
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Table of Contents
Chapter 1
Impact of DNA Methylation on Health and Disease...............................................1
Manel Esteller
Chapter 2
Uses of DNA Methylation in Cancer Diagnosis and
Risk Assessment......................................................................................................11
Carmen Jerónimo, Rui Henrique, and David Sidransky
Chapter 3
DNA Methylation in X Inactivation, Imprinting, and Associated Diseases..........27
Maria Rosaria Matarazzo, Maria Strazzullo, and Maurizio D’Esposito
Chapter 4
Studying Mammalian DNA Methylation: Bisulfite Modification..........................53
Susan J. Clark
Chapter 5
Bisulfite PCR-Based Techniques for the Study of DNA Methylation...................65
James G. Herman
Chapter 6
Microarray Analysis of DNA Methylation Targets Identified by
Methyl-CpG-Binding Proteins.................................................................................73
Masahiko Shiraishi, Michael W.-Y. Chan, and Tim H.-M. Huang
Chapter 7
Arbitrarily Primed-PCR and Related DNA Methylation Methodologies..............85
Jordi Frigola, Maria F. Paz, Manel Esteller, and Miguel A. Peinado
Chapter 8
Discovering DNA Methylation Differences with Restriction
Landmark Genomic Scanning.................................................................................95
Christoph Plass, Laura J. Rush, Dominic J. Smiraglia, and
Joseph F. Costello
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Chapter 9
Quantitative Determination of 5-Methylcytosine DNA Content:
HPCE and HPLC...................................................................................................113
Mario F. Fraga and Manel Esteller
Chapter 10
Qualitative Determination of 5-Methylcytosine and Other Components
of the DNA Methylation Machinery: Immunofluorescence and
Chromatin Immunoprecipitation...........................................................................121
Jesus Espada, Esteban Ballestar, and Manel Esteller
Chapter 11
Mouse Models for the Study of DNA Methylation..............................................137
Nicole M. Sodir and Peter W. Laird
Chapter 12
DNA Demethylating Agents: Concepts................................................................151
Jonathan C. Cheng, Daniel J. Weisenberger, and Peter A. Jones
Chapter 13
DNA Demethylating Agents: Preclinical Evaluation as Anticancer Agents........169
Robert Brown
Chapter 14
DNA Demethylating Agents: Clinical Uses..........................................................183
Michael Lübbert, Jens Hasskarl, and Rainer Claus
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1 Impact of DNA
Methylation on Health
and Disease
Manel Esteller
CONTENTS
The Relevance of DNA Methylation to Human Biology,
Clinicopathological Syndromes, and Experimental Models.....................................1
DNA Methylation in Physiological Conditions............................................1
DNA Methylation in Cancer.........................................................................2
Hypermethylation of Tumor Suppressor Genes..................................2
Using DNA Hypermethylation in Cancer Management.....................3
Global Genomic Hypomethylation......................................................3
DNA Methylation in Immunology................................................................4
DNA Methylation in Neurosciences, Cardiovascular Research,
Metabolic Diseases, Imprinting Disorders, Development, and Cloning......5
Methods Available for the Study of DNA Methylation............................................5
Conclusions and Thoughts........................................................................................6
References..................................................................................................................7
THE RELEVANCE OF DNA METHYLATION TO
HUMAN BIOLOGY, CLINICOPATHOLOGICAL
SYNDROMES, AND EXPERIMENTAL MODELS
DNA METHYLATION IN PHYSIOLOGICAL CONDITIONS
We can lump within the scope of the enigmatic word of “epigenetics” all the heritable
changes in gene expression patterns that are based on factors other than straightfor-
ward DNA sequences. The mechanisms controlling epigenetics are complex and we
have only just begun to get our first glimpses of their nature. For example, chromatin
structure, controlled by the patterns of acetylation and methylation of the histone
proteins around the regulatory regions of genes (Jenuwein and Allis, 2001), is one
critical layer of epigenetics [1]. However, at a deeper level still, the most “genetic”
of all epigenetic modifications is DNA methylation [2].
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