Abstract 3920: Understanding the molecular nature of cancer cell lines

Abstract

Abstract Large-scale cancer genome programs have generated rich data of genetic abnormalities observed in thousands of clinical patient tumors, which provides a major opportunity to develop a landscape of molecular aberrations across tumor types and propose new therapeutic targets. Although human tumor cell lines have been important tools for the cancer researcher for decades, there is a lack of bio-functional validation of genetic alterations and systematic molecular characterization across commonly used cell lines in this genomic age. To meet the need of applying cancer genome knowledge to facilitate basic and translational cancer research, an updated and accurate knowledge of the cell lines in use, particularly from a molecular viewpoint, is critical for in vitro studies. Here, we show systematic molecular characterization and clustering of 90 authenticated human tumor cell lines, which represent the most common human cancer types found in the clinic, such as lung, breast, colon, pancreatic, skin cancer and so on. By next generation sequencing and molecular profiling, those tumor cell lines were fully analyzed to capture the driver gene mutations, DNA copy number variations, gene expressions, protein expressions and relevant cell signaling pathway activations. In addition to driver mutations such as BRAF V600, KRAS G12, PI3K E545 and EGFR T790, the gene copy number amplifications of AKT, FGFR, MET, ERBB2 and deletion of PTEN are presented in this work. Moreover, correlating with the verified genetic alternations, the endogenous basal levels of protein expression and signaling pathway activations within the cells were analyzed by western blot and immunofluorescence staining. A set of 6 wild type control cell lines that were derived from either normal tissues or tumors were characterized in parallel. Furthermore, live cell growth kinetics was continually monitored by label-free cell based assay. Finally, the cell lines are clustered into 10 genetic alteration panels according to driver genes, critical protein kinases, or key components of signaling pathways. Cell lines are essential models for progressing our understanding of the cancer genome, as they allow for the functional and biological validation of the genetic alterations proposed by NGS data. The genetic alteration tumor cell panels and their molecular signature profiles provide powerful tools to accelerate the discoveries in basic cancer research, compound screening, biomarker selection, pathway analysis, and targeted therapeutic development. Citation Format: Lysa A. Volpe, Anupreet Bal, John Foulke, Michael Jackson, Luping Chen, Fang Tian. Understanding the molecular nature of cancer cell lines. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3920. doi:10.1158/1538-7445.AM2014-3920