Abstract 2993: Comparison of copy number variation using exome sequencing and affymetrix SNP6.0 genotype array in human cancer cell lines

Whole exome sequencing has been used successfully as a cost effective and unbiased method in the detection of single nucleotide variants (SNVs) in the coding regions of the human genome. Its application in identifying another class of genetic variability - copy number variation (CNV) - has been hindered by numerous factors including inconsistent exome capture probe specificity and efficiency for the target regions, discontinuous targets, and variable exon lengths etc. In the current work, we applied ExomeCNV, a depth-of-coverage based statistical analysis method developed by Sathirapongsauti et. al., to exome NGS data from a larger collection of cancer cell lines. The exomes were captured using Agilent SureSelect Human All Exon Kit and sequenced on the average depth of 70x using the Illumina HiSeq platform. To control for sequence coverage biases introduced by the capture technology, CNVs for each cancer cell line are presented as a ratio to a baseline control constructed using pooled samples processed in the same manner. Genotyping arrays are standard methods of choice for CNV discovery in cancer cell lines from the Cancer Genome Project by the Sanger Institute and the Cancer Cell Line Encyclopedia project by the Broad Institute. We obtained Affymetrix SNP6.0 genotype data for the cancer cell lines from these two sources. CNVs detected from exome sequencing were compared with those discovered from genotyping arrays in the same set of cancer cell lines. We present here a comprehensive comparison of the cancer cell line gene copy number determination from exome sequencing and genotyping methods. Our results indicate that, with sufficient exome coverage and properly constructed controls, copy number detection using exome data is a valuable alternative to genotype based approach. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2993. doi:1538-7445.AM2012-2993