Abstract 923: Separating the wheat from the chaff: A first look at the Cancer Cell Lines Encyclopedia sequencing data

Comprehensive characterization of cancer genomic alterations and understanding their functional roles are important steps in the development of personalized cancer treatments. The Cancer Cell Lines Encyclopedia project aims to relate genomic alterations to drug sensitivity of cancer cells. Cancer cell lines are indispensable resource for researchers because of their convenience for high-throughput profiling and availability for follow-up experiments. We sequenced the coding regions of 1645 genes in over 800 cancer cell lines representing 32 different tumor types. Genes were selected on their likelihood to be cancer-related and sequenced using next-generation Illumina technology after hybrid selection of exonic regions. Although, the absence of matched normal cell lines precludes direct distinction of somatic from germline mutations, we were able to select a subset of mutations highly enriched in somatic events combining the following three approaches: subtraction of known polymorphisms, prediction of strongly detrimental mutations (including computational predictions of amino acid substitutions’ effects on protein function) and detection of abnormal linkage disequilibrium patterns for recurring mutations. We then searched for the three independent indicators of the potential involvement of mutated genes in cancer: the presence of an unusually high fraction of strongly damaging mutations within a gene, statistically significant deviation of distribution of mutations between cancer types from random expectation and clustering of mutations within a gene. Combined analysis of these lines of evidence revealed both known and novel potential tumor suppressors and oncogenes. These data should become an import resource for cancer researchers in their search for personalized cancer therapies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 923. doi:10.1158/1538-7445.AM2011-923