Abstract
The application of SNP array technology to the analysis of cancer genomes has greatly advanced our knowledge of the incidence and functional consequences of acquired genomic copy number aberrations (aCNA) and LOH in various malignancies. The major challenges of using SNP arrays are accurately identifying acquired genomic DNA aberrations in the raw array data with very high sensitivity and specificity and meaningfully assessing the associations between these aberrations and biological characteristics or patient outcomes. Critical to the success and valid interpretation of data derived from SNP array profiling are (1) the purity of cells used as a source of template DNA; (2) the analysis of paired DNA samples (tumor and normal); (3) use of validated software tools for data analysis; (4) access to an acceptable gold standard for aCNA and LOH, including FISH data, cytogenetic results, and Q-PCR data; and (5) statistical support to employ or develop algorithmic approaches to SNP array data analysis. Overcalling of lesions including lack of validation and undercalling of lesions that display low fractional allelic representations are common problems. This guide should help the reader establish this powerful technology in the laboratory and aims to stimulate transition of SNP array profiling into clinical applications.
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Further Readings
Affymetrix Genotyping Console 2.0 User Manual pg 70, available by request through Affymetrix (1-888-DNA-CHIP)
Affymetrix Genotyping Console 2.0 User Manual pg 55, available by request through Affymetrix (1-888-DNA-CHIP)
“dChip Software,” http://sites.google.com/site/dchipsoft/home. Accessed 7 Sept 2011
“Copy number analysis,” http://sites.google.com/site/dchipsoft/snp-array-analysis/loh-and-copy-number-analysis/copy-number-analysis. Accessed 13 Sept 2011
“Adjust batch and individual effect,” http://sites.google.com/site/dchipsoft/snp-array-analysis/loh-and-copy-number-analysis/adjust-batch-and-individual-effect. Accessed 7 Sept 2011
Acknowledgments
We acknowledge the important contributions to this protocol and to the LOH tool/PLUT development by Mr. Sajid Shakhan and Ms. Whitney Wright.
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Ouillette, P.D., Shedden, K.A., Li, C., Malek, S.N. (2013). 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. In: Banerjee, D., Shah, S. (eds) Array Comparative Genomic Hybridization. Methods in Molecular Biology, vol 973. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-281-0_7
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DOI: https://doi.org/10.1007/978-1-62703-281-0_7
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