FGFR2 fusion protein-driven mouse models of intrahepatic cholangiocarcinoma unveil a necessary role for Erk signaling

Four structurally different FFs were expressed in Tp53-/- mouse liver organoids. The tumorigenic properties of genetically-modified liver organoids were assessed by intrahepatic or subcutaneous transplantation in immuno-deficient mice. RNA was extracted from tumors and subjected to RNAseq. Transcriptional profiling identified up/down-regulated signatures shared between human and mouse cholangiocarcinomas driven by FGFR2 fusion proteins. Overall design: Tumors diagnosed as cholangiocarcinoma, obtained upon s.c. or intra-hepatic transplantation of Tp53 null liver organoids engineered to express either FGFR2-BICC1 or FGFR2-TACC3, were excised and subjected to RNAseq. RNAseq data were analyzed in order to discover transcriptional similarities between human and mouse cholangiocarcinomas driven by oncogenic FGFR2 fusion proteins.