Detection of FGFR2 Fusions in Plasma RNA from patients with Cholangiocarcinoma
Cholangiocarcinoma (CCA) is a lethal cancer of the bile duct with 20% five-year survival rate. Fibroblast Growth Receptor 2 (FGFR2) gene fusions are present in 13-17% of intrahepatic CCA. Recent clinical trials with FGFR inhibitors have shown promising results. However, finding patients whose tumors carry the FGFR2 fusion remains challenging because tumor biopsies are difficult to obtain in CCA. An alternative is to use non-invasive blood-based diagnostics based on tumor-derived nucleic acids shed into circulation. We have devised a novel sequencing approach to detect FGFR2 fusions in RNA from plasma, using TArgeted DIgital Sequencing (TARDIS). We tested the feasibility of our approach using RNA from formalin-fixed paraffin-embedded (FFPE) tissue samples. The approach was feasible with a minimal input of 5ng of FFPE RNA. Future steps involve analytical and clinical validation using plasma samples.