Abstract
Cancer represents the phenotypic end point of multiple genetic lesions that endow cells with a full range of biological properties required for tumorigenesis. Among the hallmark features of the cancer genome are recurrent regional gains and losses that, upon detailed characterization, have provided highly productive discovery paths for new oncogenes and tumor suppressor genes. In this study, we describe the use of an oligonucleotide-based microarray platform and development of requisite assay conditions and bioinformatic mining tools that permits high-resolution genome-wide array-comparative genome hybridization profiling of human and mouse tumors. Using a commercially available 60-mer oligonucleotide microarray, we demonstrate that this platform provides sufficient sensitivity to detect single-copy difference in gene dosage of full complexity genomic DNA while offering high resolution. The commercial availability of the microarrays and associated reagents, along with the technical protocols and analytical tools described in this report, should provide investigators with the immediate capacity to perform DNA analysis of normal and diseased genomes in a global and detailed manner.
Highlights
Viding that high background probes are eliminated by empirical and bioinformatic means.3 highly effective, the full potential of cDNA microarrays has been constrained by currently available validated cDNA repositories
We examined the utility of long oligonucleotide (60-mer) microarrays (Agilent Technologies) for array-Comparative genomic hybridization (CGH)
This study reports the successful implementation of technical protocols and analytical tools for an array-CGH platform that uses commercially available microarrays composed of long oligonucleotide probes
Summary
Viding that high background probes are eliminated by empirical and bioinformatic means.3 highly effective, the full potential of cDNA microarrays has been constrained by currently available validated cDNA repositories. We describe assay conditions and bioinformatic tools that enhance the utility of oligo-based microarray platforms in genome-wide DNA copy number analyses of human and mouse cancers.
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