Multiple functions of a glioblastoma fusion oncogene
Ivan Babic, Paul S. Mischel
Ivan Babic, Paul S. Mischel
Published January 9, 2013
Citation Information: J Clin Invest. 2013;123(2):548-551. https://doi.org/10.1172/JCI67658.
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Commentary

Multiple functions of a glioblastoma fusion oncogene

Abstract

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.

Authors

Ivan Babic, Paul S. Mischel

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Figure 1

A tandem duplication event results in the formation of an FGFR3-TACC3 fusion product.

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A tandem duplication event results in the formation of an FGFR3-TACC3 fu...
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).