Table Of ContentM M B ™
ethods in olecular iology
Series Editor
John M. Walker
School of Life Sciences
University of Hertfordshire
Hatfield, Hertfordshire, AL10 9AB, UK
For other titles published in this series, go to
www.springer.com/series/7651
Cancer Susceptibility
Methods and Protocols
Edited by
Michelle Webb
Faculty of Medical and Human Sciences, School of Clinical Laboratory Sciences,
University of Manchester, Manchester, UK
Editor
Michelle Webb, Ph.D.
Faculty of Medical and Human Sciences
School of Clinical Laboratory Sciences
University of Manchester,
Manchester, UK
[email protected]
ISSN 1064-3745 e -ISSN 1940-6029
ISBN 978-1-60761-758-7 e-ISBN 978-1-60761-759-4
DOI 10.1007/978-1-60761-759-4
Springer New York Dordrecht Heidelberg London
Library of Congress Control Number: 2010930786
© Springer Science+Business Media, LLC 2010
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Preface
Over the past 2 decades, spectacular advances have been made in understanding the
molecular genetics of cancer. One of the major objectives of modern day cancer research
is to identify genes that when mutated result in an increased susceptibility to the disease.
This knowledge can be translated into clinical practice where screening for a predisposi-
tion becomes part of an at-risk patient’s surveillance and management strategy. An exam-
ple where this has been successful is in the management of hereditary breast cancer.
Following the identification of the breast cancer susceptibility genes, BRCA1 and BRCA2,
in the early 1990s, genetic screens that estimate a patient’s risk have now become avail-
able. While this success is now being extended to other cancer disorders, more genes need
to be identified, characterized, and screens need to be developed. A book that brings
together the most recent technological developments for identifying and screening cancer
susceptibility genes is therefore very timely. The book is separated broadly into two parts.
The first part, gene identification, informs scientists working at identifying novel cancer
susceptibility genes, while the second part deals with mutation screening technologies that
aid scientists and clinicians working to translate this knowledge into the clinic.
Manchester, UK Michelle Webb
v
Contents
Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v
Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix
Part I IdentIfyIng CanCer SuSCePtIbIlIty geneS
1 The Identification of Colon Cancer Susceptibility
Genes by Using Genome-Wide Scans .................................. 3
Denise Daley
2 Prioritizing Candidate Genetic Modifiers of BRCA1 and BRCA2
Using a Combinatorial Analysis of Global Expression and
Polymorphism Association Studies of Breast Cancer ....................... 23
Logan C. Walker and Amanda B. Spurdle
3 Microarray-Based Comparative Genomic Hybridization
(Array-CGH) as a Useful Tool for Identifying Genes Involved
in Glioblastoma (GB).............................................. 35
Yolanda Ruano, Manuela Mollejo, Angel Rodríguez de Lope,
José Luis Hernández-Moneo, Pedro Martínez, and Bárbara Meléndez
4 Multiplex Amplifiable Probe Hybridization (MAPH) Methodology
as an Alternative to Comparative Genomic Hybridization (CGH)............. 47
Ludmila Kousoulidou, Carolina Sismani, and Philippos C. Patsalis
5 Utilizing Saccharomyces Cerevisiae to Identify
Aneuploidy and Cancer Susceptibility Genes............................. 73
Erin D. Strome and Sharon E. Plon
6 Computational Identification of Cancer Susceptibility Loci.................. 87
Marko Laakso, Sirkku Karinen, Rainer Lehtonen,
and Sampsa Hautaniemi
7 Digital Candidate Gene Approach (DigiCGA) for
Identification of Cancer Genes ....................................... 105
Meng-Jin Zhu, Xiang Li, and Shu-Hong Zhao
Part II SCreenIng CanCer SuSCePtIbIlIty geneS
8 The Use of Denaturing High Performance Liquid Chromatography
(DHPLC) for Mutation Scanning of Hereditary Cancer Genes............... 133
Deborah J. Marsh and Viive M. Howell
9 Enhanced Mismatch Mutation Analysis: Simultaneous Detection of
Point Mutations and Large Scale Rearrangements by Capillary
Electrophoresis, Application to BRCA1 and BRCA2 ...................... 147
Claude Houdayer, Virginie Moncoutier, Jérôme Champ, Jérémie Weber,
Jean-Louis Viovy, and Dominique Stoppa-Lyonnet
vii
viii Contents
10 Economical Protocol for Combined Single-Strand Conformation
Polymorphism and Heteroduplex Analysis on a Standard Capillary
Electrophoresis Apparatus........................................... 181
Piotr Kozlowski and Wlodzimierz J. Krzyzosiak
11 Mutational Screening of hMLH1 and hMSH2 that Confer Inherited
Colorectal Cancer Susceptibility Using Denature Gradient Gel
Electrophoresis (DGGE) ........................................... 193
Tao Liu
12 s-RT-MELT: A Novel Technology for Mutation Screening.................. 207
Jin Li and G. Mike Makrigiorgos
13 Zoom-In Array Comparative Genomic Hybridization (aCGH)
to Detect Germline Rearrangements in Cancer Susceptibility Genes ........... 221
Johan Staaf and Åke Borg
14 Development of a Scoring System to Screen for BRCA1/2 Mutations.......... 237
Gareth R. Evans and Fiona Lalloo
15 Use of Splicing Reporter Minigene Assay to Evaluate
the Effect on Splicing of Unclassified Genetic Variants ..................... 249
Pascaline Gaildrat, Audrey Killian, Alexandra Martins,
Isabelle Tournier, Thierry Frébourg, and Mario Tosi
16 Functional Analysis of Human BRCA2 Variants Using
a Mouse Embryonic Stem Cell-Based Assay ............................. 259
Sergey G. Kuznetsov, Suhwan Chang, and Shyam K. Sharan
17 Developing Functional Assays for BRCA1 Unclassified Variants .............. 281
Michelle Webb
Index.............................................................. 293
Contributors
Åke borg • Department of Oncology, Clinical Sciences, CREATE Health Strategic
Centre For Translational Cancer Research, Lund University, Lund, Sweden
Jérôme ChamP • Service de Génétique Oncologique, Institut Curie Hôpital,
Paris, France
Suhwan Chang • Center for Cancer Research, Mouse Cancer Genetics Program,
National Cancer Institute at Frederick, Frederick, MD, USA
denISe daley • Department of Medicine, St . Paul’s Hospital, University of British
Columbia, Vancouver, BC, Canada
gareth r. evanS • Medical Genetics Research Group and Regional Genetics Service,
St Mary’s Hospital, University of Manchester and Central Manchester and
Manchester Children’s University Hospitals NHS Trust, Manchester, UK
thIerry frébourg • Faculty of Medicine Department of Genetics and Institute for
Biomedical Research, Rouen University Hospital, Inserm U614, IFRMP, University
of Rouen, Northwest Canceropole, Rouen, France
PaSCalIne gaIldrat • Faculty of Medicine Department of Genetics and Institute for
Biomedical Research, Rouen University Hospital, Inserm U614, IFRMP, University
of Rouen, Northwest Canceropole, Rouen, France
SamPSa hautanIemI • Computational Systems Biology Laboratory, Institute of
Biomedicine and Genome-Scale Biology Research Program, University of Helsinki,
Helsinki, Finland
JoSé luIS hernández-moneo • Department of Neurosurgery, Virgen de la Salud
Hospital, Toledo, Spain
Claude houdayer • Service de Génétique Oncologique, Institut Curie Hôpital,
Paris, France; Faculté de Sciences Pharmaceutiques et Biologiques, Université Paris
Descartes, Paris, France
vIIve m. howell • Royal North Shore Hospital, Kolling Institute of Medical
Research, University of Sydney, Sydney, NSW, Australia
SIrkku karInen • Computational Systems Biology Laboratory, Institute of
Biomedicine and Genome-Scale Biology Research Program, University of Helsinki,
Helsinki, Finland
audrey kIllIan • Faculty of Medicine Department of Genetics and Institute for
Biomedical Research, Rouen University Hospital, Inserm U614, IFRMP,
University of Rouen, Northwest Canceropole, Rouen, France
ludmIla kouSoulIdou • Department of Cytogenetics and Genomics, The Cyprus
Institute of Neurology and Genetics, Nicosia, Cyprus
PIotr kozlowSkI • Laboratory of Cancer Genetics, Institute of Bioorganic Chemistry,
Polish Academy of Sciences, Poznań, Poland
wlodzImIerz J. krzyzoSIak • Laboratory of Cancer Genetics, Institute of Bioorganic
Chemistry, Polish Academy of Sciences, Poznań, Poland
ix
x Contributors
Sergey g. kuznetSov • Center for Cancer Research, Mouse Cancer Genetics
Program, National Cancer Institute at Frederick, Frederick, MD, USA; Institute
for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland
marko laakSo • Computational Systems Biology Laboratory, Institute of
Biomedicine and Genome-Scale Biology Research Program, University of Helsinki,
Helsinki, Finland
fIona lalloo • Medical Genetics Research Group and Regional Genetics Service,
St Mary’s Hospital, University of Manchester and Central Manchester and
Manchester Children’s University Hospitals NHS Trust, Manchester, UK
raIner lehtonen • Department of Biological and Environmental Sciences,
Metapopulation Research Group, University of Helsinki, Helsinki, Finland
JIn lI • Division of Genomic Stability and Division of DNA Repair and
Medical Physics and Biophysics, Department of Radiation Oncology,
Harvard Medical School, Dana Farber Cancer Institute and Brigham and
Women’s Hospital, Boston, MA, USA
XIang lI • Key Laboratory of Agricultural Animal Genetics, Breeding and
Reproduction of Ministry of Education, Huazhong Agricultural University,
Wuhan, China
tao lIu • Cancer Centre Karolinska, Karolinska Institute, Stockholm, Sweden
g. mIke makrIgIorgoS • Division of Genomic Stability and Division of DNA
Repair and Medical Physics and Biophysics, Department of Radiation Oncology,
Harvard Medical School, Dana Farber Cancer Institute and Brigham and
Women’s Hospital, BostonMA, USA
deborah J. marSh • Royal North Shore Hospital, Kolling Institute of Medical
Research, University of Sydney, Sydney,NSW, Australia
Pedro martínez • Department of Genetics, Virgen de la Salud Hospital, Toledo,
Spain
aleXandra martInS • Faculty of MedicineDepartment of Genetics and Institute for
Biomedical Research, Rouen University Hospital, Inserm U614, IFRMP,
University of Rouen, Northwest Canceropole, Rouen, France
bárbara meléndez • Molecular Pathology Research Unit, Virgen de la Salud
Hospital, Toledo, Spain
manuela molleJo • Department of Pathology and Molecular Pathology Research
Unit, Virgen de la Salud Hospital, Toledo, Spain
vIrgInIe monCoutIer • Service de Génétique Oncologique, Institut Curie Hôpital,
Paris, France
PhIlIPPoS C. PatSalIS • Department of Cytogenetics and Genomics, The Cyprus
Institute of Neurology and Genetics, Nicosia, Cyprus
Sharon e. Plon • Department of Molecular and Human Genetics, Baylor College of
Medicine, Houston,TX, USA
angel rodríguez de loPe • Department of Neurosurgery, Virgen de la Salud
Hospital, Toledo, Spain
yolanda ruano • Molecular Pathology Research Unit, Virgen de la Salud Hospital,
Toledo, Spain
