Identification Of Somatic Mutations In Esophageal Squamous Cell Carcinoma And Corresponding Xenograft By Next-Generation Sequencing

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL The genomes of all cancer cells carry somatic mutations, including both passenger and driver mutations. Driver mutations, which are implicated in oncogenesis, are most likely preserved in xenografted tumor cells in immunedeficient mice. Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive carcinomas in the gastrointenstinal tract. It is prevalent in the developing world and associated with substantial morbidity and mortality. Molecular mechanisms contributing to initiation and progression of ESCC are still poorly understood. Systematic identification of genetic variations and putative driver mutations may lead to understanding of pathogenesis of the disease. In this study, using next-generation sequencing we performed exome sequencing of eight paired Chinese esophageal squamous cell carcinoma and xenograft. Comparing with control genomes obtained from case-matched peripheral blood cells, we identified a wide variety of somatic variations in both primary and xenograft tumors, including TP53, RGMA, MUC4, TCEAL6, PRSS3, etc. Moreover, we found that mouse sequences accounted for a significant fraction of sequence reads from xenograft samples. Excluding these mouse sequences significantly improved the accuracy of mutation detection in xenograft samples. Overall, our findings shed a light on important somatic mutations involved in ESCC. In addition, comparison between primary and xenograft tumors may lead to identification of driver mutations that confer growth advantage. These mutations represent therapeutic opportunities for development of targeted therapy. 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 2351. doi:1538-7445.AM2012-2351