Biomedical Engineering Reference
In-Depth Information
High-Resolution Analysis
of Genomic Copy Number
Changes
Mario Hermsen
1
, Jordy Coffa
2
, Bauke Ylstra
3
, Gerrit Meijer
2
, Hans Morreau
4
,
Ronald van Eijk
4
,JanOosting
4
and Tom van Wezel
4
1
Department Otorrinolaringologıa, Instituto Universitario de Oncologıa del Principado de Asturias,
Oviedo, Spain
2
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands
3
Microarray Facility, VU University Medical Center, Amsterdam, The Netherlands
4
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
1.1 Introduction
The analysis of DNA copy number changes throughout the whole genome started with
the introduction of comparative genomic hybridization (CGH), first described in 1992 by
Kallioniemi
et al
. [1]. This elegant technique was based on the competitive hybridization
of two pools of fluorescent-labeled probes, one made up of whole-genome DNA of a test
and another of a control sample, to a metaphase preparation of normal chromosomes. Along
each chromosome, the fluorescent intensity of the test DNA was quantified and compared
with the control intensity, resulting in 'relative copy number karyotypes.'
It appeared to be very difficult to reproduce the method in laboratories not specialized
in chromosome techniques. Only after the publication of an article reviewing all steps
in great detail did CGH become more widely applied [2], especially in cancer genetics.
The possibility of using DNA obtained from formalin-fixed and paraffin-embedded (FFPE)
samples opened up the way for retrospective studies of tumors with clinical follow-up data,
enabling the identification of genetic changes related to tumor progression, invasion and
metastasis [3].
