Abstract 4919: Tumor heterogeneity represented in human cancer cell lines

Abstract

EGFR has been found frequently mutated in human cancers, and more than 10% lung cancer patients associated with EGFR mutation. In addition, several critical mutations within the EGFR have been shown as gain of function mutations or can cause drug resistance to the EGFR inhibitors. A panel of ATCC tumor cell lines has been characterized for EGFR mutation and EGFR signaling pathway. Particularly, lung cell line NCI-H1975, which contains both drug sensitive mutation EGFR p.L858R and drug resistant mutation p.T790M, has displayed a resistance to EGFR inhibitor.Overall, NCI-H1975 cell line can be used as a nice model to study drug resistance, as well as to screen novel EGFR inhibitors that overcome the p.T790M-mediated resistance. Moreover, we have used next generation sequencing to analyze the mutation allelic frequency of both mutations, and observed tumor heterogeneity within this cell line. Impact of cell passage numbers on the mutation allele frequency of the cell line was also examined. Furthermore, a novel single cell western blot assay has been used to analyze the EGFR mutation, EGFR protein expression and downstream signaling within individual cells of three lung cancer cell lines at the single cell level. Collectively, NCI-H1975 cell line represents the acquired drug resistance found in clinical cancer patients, and this study demonstrates the tumor heterogeneity represented in human cell lines. Citation Format: Lysa-Anne Volpe, John Foulke, Michael Jackson, Luping Chen, David H. Randle, Hannah J. Gitschier, Kelly Gardner, Fang Tian. Tumor heterogeneity represented in human cancer cell lines. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4919. doi:10.1158/1538-7445.AM2015-4919