Table Of ContentM M B ™
ETHODS IN OLECULAR IOLOGY
Series Editor
John M. Walker
School of Life Sciences
University of Hertfordshire
Hat fi eld, Hertfordshire, AL10 9AB, UK
For further volumes:
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Array Comparative Genomic
Hybridization
Protocols and Applications
Edited by
Diponkar Banerjee
Department of Pathology and Laboratory Medicine, The Ottawa Hospital, Ottawa, Canada
Sohrab P. Shah
Department of Molecular Oncology, BC Cancer Agency, Vancouver, Canada
Editors
Diponkar Banerjee Sohrab P. Shah
Department of Pathology Department of Molecular Oncology
and Laboratory Medicine The Ottawa Hospital BC Cancer Agency
Ottawa, Canada Vancouver, Canada
ISSN 1064-3745 ISSN 1940-6029 (electronic)
ISBN 978-1-62703-280-3 ISBN 978-1-62703-281-0 (eBook)
DOI 10.1007/978-1-62703-281-0
Springer New York Heidelberg Dordrecht London
Library of Congress Control Number: 2012956547
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Preface
The earliest descriptions of human chromosomes in the late 1800s by Arnold and Flemming
were the beginning of the genomics revolution now upon us. This book on “Array
Comparative Genomic Hybridization: Protocols and Applications” explores the scope of
what is now possible in documenting abnormalities associated with several types of human
cancers. While the technology for interrogating the human genome continues to evolve,
refi nement of comparative genomic hybridization (CGH) using array CGH and related
technologies have provided enormous insight into human cancers at an affordable scale in
research and clinical laboratories.
As stated in Chapter 2 by Ewa Przybytkowski and colleagues, “Array CGH is a mature
technology with low-cost competitive products, stable commercially produced software,
and standardized protocols and therefore provides a low-cost, robust, and more easily
accessible technology readily available to most wet lab scientists. In addition, aCGH allows
the accurate characterization of gene copy number using as little as 0.5 μ g of genomic
DNA.” Although costs of next generation sequencing is coming down rapidly, the true cost
including bioinformatics support and computing power is daunting for most investigators
and clinical laboratories. The challenge for diagnostic laboratories is also to produce results
within a clinically meaningful time frame. Array CGH thus is not only cost effective as data
analysis is simpler, it can produce clinically relevant data in a timely manner.
Some of the highlights include Chapter 3 in which Martin Hirst discusses the variety of
sequence-based DNA methylation techniques to generate DNA methylation maps from normal
and abnormal human tissue. Lisa Shaffer and colleagues discuss the two basic types of genomic
microarrays in Chapter 4 : Comparative genomic hybridization-based arrays (aCGH) and single
nucleotide polymorphism-based (SNP) arrays. They describe benefi ts and challenges of each
method in assessing Myelodysplastic Syndrome, and provide guidance in the interpretation of
the results and reporting of the diagnostic or prognostic implications to physicians.
A variety of human neoplasia are covered in this book, including breast cancer, acute
and chronic myeloid leukemia, chronic lymphocytic leukemia, diffuse large B cell lym-
phoma, mantle cell lymphoma, malt and marginal zone lymphomas, mycosis fungoides and
Sezary syndrome, adult T-cell leukemia/lymphoma, cutaneous anaplastic large cell lym-
phoma, HIV-related B-cell lymphomas, pediatric osteosarcoma, Wilm’s tumor, childhood
myelodysplastic syndromes, adenocarcinoma of lung, and brain tumors.
Finally, two outstanding chapters have been contributed by Oscar Rueda and colleagues
and Gavin Ha on computational aspects of assessing copy number alteration and variation.
We are indeed honored by the generous contributions of many of the leaders in the
fie ld who have provided overviews of the technologies and many have provided detailed
step-by-step protocols to allow the readers to follow and learn these techniques for their
own use in research or clinical diagnostic laboratories.
Ottawa, Canada Diponkar Banerjee
Vancouver, Canada Sohrab P. Shah
v
Contents
Preface. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v
Contributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix
1 Array Comparative Genomic Hybridization: An Overview
of Protocols, Applications, and Technology Trends. . . . . . . . . . . . . . . . . . . . . 1
Diponkar Banerjee
2 Ultradense Array CGH and Discovery of Micro-Copy
Number Alterations and Gene Fusions in the Cancer Genome. . . . . . . . . . . . . 15
Ewa Przybytkowski, Adriana Aguilar-Mahecha, Sheida Nabavi,
Peter J. Tonellato, and Mark Basik
3 Epigenomics: Sequencing the Methylome. . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
Martin Hirst
4 Application of Array Comparative Genomic Hybridization
in Chronic Myeloid Leukemia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
Seonyang Park, Youngil Koh, Seung-Hyun Jung,
and Yeun-Jun Chung
5 The Use of Cytogenetic Microarrays in Myelodysplastic
Syndrome Characterization. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
Lisa G. Shaffer, Blake C. Ballif, and Roger A. Schultz
6 CGH Protocols: Chronic Lymphocytic Leukemia. . . . . . . . . . . . . . . . . . . . . . 87
Esteban Braggio, Rafael Fonseca, and Neil E. Kay
7 Analysis of Acquired Genomic Copy Number Aberrations
and Regions of Loss of Heterozygosity in Acute Myelogenous
Leukemia Genomes Using Affymetrix SNP 6.0 Arrays
and Supporting Software Tools. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
Peter D. Ouillette, Kerby A. Shedden, Cheng Li, and Sami N. Malek
8 Clinical Applications of BAC Array-CGH to the Study
of Diffuse Large B-Cell Lymphomas. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121
Cristina Robledo, Juan Luis García, and Jesús M. Hernández
9 Genomic Profiling of Mantle Cell Lymphoma. . . . . . . . . . . . . . . . . . . . . . . . . 147
Melissa Rieger Menanteau and Jose A. Martinez-Climent
10 Copy Number Analysis in EBV-Positive Nodal Peripheral
T Cell Lymphoma, Unspecified. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165
Kyusam Choi, Hyunjeong Ju, and Young Hyeh Ko
11 Mycosis Fungoides and Sézary Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175
Blanca Espinet and Rocío Salgado
12 Array CGH Reveals Clonal Evolution of Adult T-Cell
Leukemia/Lymphoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189
Akira Umino and Masao Seto
vii
viii Contents
13 Array-CGH Analysis of Cutaneous Anaplastic Large Cell Lymphoma . . . . . . . 197
K. Szuhai, R. van Doorn, C.P. Tensen, and Van Kester
14 Genome-Wide DNA Profiling of HIV-Related B-Cell Lymphomas. . . . . . . . . 213
Andrea Rinaldi, Daniela Capello, Emanuele Zucca,
Gianluca Gaidano, and Francesco Bertoni
15 Array Comparative Genomic Hybridization in Osteosarcoma . . . . . . . . . . . . . 227
Bekim Sadikovic, Paul C. Park, Shamini Selvarajah,
and Maria Zielenska
16 Comparative Genomic Hybridization of Wilms’ tumor . . . . . . . . . . . . . . . . . . 249
Shahrad Rod Rassekh and Evica Rajcan-Separovic
17 Array-CGH in Childhood MDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 267
Marcel Tauscher, Inka Praulich, and Doris Steinemann
18 Nonfamilial Breast Cancer Subtypes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 279
Markus Ringnér, Johan Staaf, and Göran Jönsson
19 Applications of Array-CGH for Lung Cancer. . . . . . . . . . . . . . . . . . . . . . . . . . 297
Kenneth J. Craddock, Wan L. Lam, and Ming-Sound Tsao
20 Array CGH in Brain Tumors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 325
Gayatry Mohapatra, Julia Sharma, and Stephen Yip
21 Finding Common Regions of Alteration in Copy Number Data . . . . . . . . . . . 339
Oscar M. Rueda, Ramon Diaz-Uriarte, and Carlos Caldas
22 Distinguishing Somatic and Germline Copy Number Events
in Cancer Patient DNA Hybridized to Whole-Genome SNP
Genotyping Arrays . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 355
Gavin Ha and Sohrab Shah
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 373
Contributors
ADRIANA AGUILAR-MAHECHA (cid:129) Department of Oncology, Lady Davis Institute,
Sir Mortimer B. Davis, Jewish General Hospital, McGill University, Montreal , QC ,
Canada
BLAKE C. BALLIF (cid:129) Signature Genomic Laboratories, PerkinElmer Inc., Spokane, WA , USA
DIPONKAR BANERJEE (cid:129) Department of Pathology and Laboratory Medicine, The Ottawa
Hospital , Ottawa , BC , Canada
MARK BASIK (cid:129) Department of Oncology, Lady Davis Institute, Sir Mortimer B. Davis,
Jewish General Hospital, McGill University, Montreal , QC , Canada
FRANCESCO BERTONI (cid:129) Fondazione per la Ricerca e la Cura sui Linfomi, IOR Institute of
Oncology Research, Lymphoma & Genomics Research Program, Bellinzona, Switzerland
ESTEBAN BRAGGIO (cid:129) Mayo Clinic Arizona, Scottsdale, AZ , USA
CARLOS CALDAS (cid:129) Department of Oncology, University of Cambridge, Cambridge, UK;
Cancer Research UK Cambridge Research Institute, Cambridge, UK; Cambridge Breast
Unit , Addenbrooke’s Hospital, Cambridge University Hospital NHS Foundation Trust ,
Cambridge, UK; NIHR Cambridge Biomedical Research Centre, Cambridge, UK;
Cambridge Experimental Cancer Medicine Centre, Cambridge, UK
DANIELA CAPELLO (cid:129) Fondazione per la Ricerca e la Cura sui Linfomi, IOR Institute
of Oncology Research, Lymphoma & Genomics Research Program , Bellinzona,
Switzerland
KYUSAM CHOI (cid:129) Samsung Biomedical Research Institute, Samsung Medical Center, Seoul ,
Korea
YEUN-JUN CHUNG (cid:129) Department of Internal Medicine, Diagnostic DNA Chip Center,
Seoul National University College of Medicine, Seoul , Korea
KENNETH J. CRADDOCK (cid:129) Department of Pathology, Toronto General Hospital University
Health Network, Toronto , ON , Canada
RAMON DIAZ-URIARTE (cid:129) Departamento de Bioquímica, Instituto de Investigaciones
Biomédicas “Alberto Sols,” Universidad Autónoma de Madrid, Madrid , Spain
BLANCA ESPINET (cid:129) Molecular Cytogenetics Laboratory, Pathology Department, Hospital del
Mar , Barcelona, Spain
RAFAEL FONSECA (cid:129) Department of Hematology/Oncology , Mayo Clinic Arizona,
Scottsdale, AZ , USA
GIANLUCA GAIDANO (cid:129) Fondazione per la Ricerca e la Cura sui Linfomi, IOR Institute of
Oncology Research, Lymphoma & Genomics Research Program , Bellinzona, Switzerland
JUAN LUIS GARCÍA (cid:129) Unidad de Diagnóstico Molecular y Celular del Cáncer, IBMCC,
Centro de Investigación del Cáncer, Universidad de Salamanca-CSIC , Salamanca,
Spain; Instituto de Estudios de Ciencias de la Salud de Castilla y León, León , Spain
GAVIN HA (cid:129) Molecular Oncology, BC Cancer Agency, Vancouver, BC , Canada
JESÚS M. HERNÁNDEZ (cid:129) Unidad de Diagnóstico Molecular y Celular del Cáncer, IBMCC,
Centro de Investigación del Cáncer, Universidad de Salamanca-CSIC , Salamanca, Spain;
Servicio de Hematología, Hospital Universitario de Salamanca, Salamanca, Spain
ix
