RNA sequencing facilitates the discovery of novel gene fusions in cancer. In this issue of the JCI, Parker et al. identify an FGFR3-TACC3 fusion oncogene in glioblastoma and demonstrate a novel mechanism of pathogenicity. A miR-99a binding site within the 3′–untranslated region (3′-UTR) of FGFR3 is lost, releasing FGFR3 signaling from miR-99a–dependent inhibition and greatly enhancing tumor progression relative to WT FGFR3. These results provide compelling insight into the pathogenicity of a novel fusion oncogene and suggest new therapeutic approaches for a subset of glioblastomas.
Here, Parker et al. demonstrate that the fusion transcript lacks a miR-99a binding site, resulting in increased expression (12). In addition, FGFR3-TACC3 fusion activates ERK and STAT3 signaling and enhances tumor progression. Previous work also demonstrated that localization of this fusion protein to the mitotic spindles promotes aneuploidy (13).