Genomic profiling of biliary tract cancer cell lines reveals molecular subtypes and actionable drug targets

Purpose: Biliary tract cancers (BTCs) carry a very poor prognosis and have no approved targeted therapies. Recent genomic profiling of primary BTCs identified a number of potentially actionable drug targets, however accurate model systems to evaluate these targets are currently lacking. The purpose of this study was to compare the genomic landscape of commonly used BTC cell lines to primary BTCs, and to utilize these models for drug target evaluation. Design: Twenty BTC cell lines were profiled by RNA-seq analysis. Results: Transcriptomic profiling of BTC cell lines identified two subtypes, enriched for epithelial and mesenchymal genes respectively, which were also identified in primary BTC. Conclusions: Cell lines harbor similar genomic alterations to primary BTCs. Integration of cell line and primary cancer data identify novel molecular subsets, and highlight specific molecular vulnerabilities in BTC. 20 biliary tract cancer cell lines were profiled by RNA-seq analysis.