Exome sequencing has been used as an efficient and cost-effective method of identifying somatic mutations in tumors. In order to evaluate the effectiveness of the current exome sequencing technology, we have conducted a comparative study to evaluate exome and whole genome sequencing (WGS) in two pairs of hepatocelluar carcinoma (HCC) tumor and match normal controls. The exome sequences were captured via Agilent SureSelect Target Enrichment System (38 MB). Both exome and WGS sequencing data were generated by the Illumina Hiseq2000 platform. The NGS results showed identical profiles of chromosomal abnormalities, including ploidy changes and loss of heterozygosity, when compared to Affymetrix SNP 6.0 microarray genotyping. The total number of variants detected in transcribed region (CCDS) in each of the four samples was comparable between exome and WGS data sets, and the genotypes concordance rate was high. The somatic mutations detected in each tumor/normal pairs different slightly between the exome and WGS platforms. We manually inspected each of the discordant mutations, and found that the most of the somatic mutations missed by exome sequencing are predictable based on gaps in SureSelect coverage. On the other hand, we have also identified somatic mutations in exome that were not detected with the WGS approach. Follow up analysis indicated that those cases were caused by no or low coverage in either tumor of normal in each pair. These cases will likely be resolved by increasing depth of coverage (beyond 30X), and as costs per read decline, it is likely WGS will become the method of choice.

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 2094. doi:1538-7445.AM2012-2094