Genomic architecture of FGFR2 fusions in cholangiocarcinoma and its implication for molecular testing
Menée à partir de l'analyse de données génétiques provenant d'un essai clinique évaluant le pemigatinib pour traiter un cholangiocarcinome de stade localement avancé ou métastatique, cette étude identifie les caractéristiques et l'architecture des fusions du gène FGFR2 présentes dans certains cholangiocarcinomes
Background : Cholangiocarcinoma (CCA) is a primary malignancy of the biliary tract with a dismal prognosis. Recently, several actionable genetic aberrations were identified with significant enrichment in intrahepatic CCA, including FGFR2 gene fusions with a prevalence of 10–15%. Recent clinical data demonstrate that these fusions are druggable in a second-line setting in advanced/metastatic disease and the efficacy in earlier lines of therapy is being evaluated in ongoing clinical trials. This scenario warrants standardised molecular profiling of these tumours.
Methods : A detailed analysis of the original genetic data from the FIGHT-202 trial, on which the approval of Pemigatinib was based, was conducted.
Results : Comparing different detection approaches and displaying representative cases, we described the genetic landscape and architecture of FGFR2 fusions in iCCA and show biological and technical aspects to be considered for their detection. We elaborated parameters, including a suggestion for annotation, that should be stated in a molecular diagnostic FGFR2 report to allow a complete understanding of the analysis performed and the information provided.
Conclusion : This study provides a detailed presentation and dissection of the technical and biological aspects regarding FGFR2 fusion detection, which aims to support molecular pathologists, pathologists and clinicians in diagnostics, reporting of the results and decision-making.
British Journal of Cancer , article en libre accès, 2022