DR-138 Genomic identification and expression of oncogenic FGFR2 structural variants.

Using mouse models, we found certain variants of the fibroblast growth factor receptor 2 gene (Fgfr2) to be strong tumor drivers. These oncogenic Fgfr2 variants all lack the last exon resulting in shortened FGFR2 proteins. Importantly, cells expressing shortened FGFR2 are very sensitive to inhibitors blocking FGFR2 signaling. Moreover, preliminary data suggest that human cancers might also recurrently harbor genetic alterations of the FGFR2 locus presumably producing shortened FGFR2. To strengthen and validate these findings, the Hartwig Medical Foundation whole-genome sequencing and RNA sequencing datasets represent valuable resources. Ultimately, these findings might refine the inclusion criteria for FGFR2-targeting precision therapies.

Daniel Zingg Netherlands Cancer Institute the Netherlands