Targetable Gene Fusions Associate With the IDH Wild-Type Astrocytic Lineage in Adult Gliomas
Gene fusions involving oncogenes have been reported in gliomas and may serve as novel therapeutic targets. Using RNA-sequencing, we interrogated a large cohort of gliomas to assess for the incidence of targetable genetic fusions. Gliomas (n = 390) were profiled using the ArcherDx FusionPlex Assay. Fifty-two gene targets were analyzed and fusions with preserved kinase domains were investigated. Overall, 36 gliomas (9%) harbored a total of 37 potentially targetable fusions, the majority of which were found in astrocytomas (n = 34). Within this lineage 11% (25/235) of glioblastomas, 12% (5/42) of anaplastic astrocytomas, 8% (2/25) of grade II astrocytomas, and 33% (2/6) of pilocytic astrocytoma harbored targetable fusions. Fusions were significantly more frequent in IDH wild-type tumors (12%, n = 31/261) relative to IDH mutants (4%; n = 4/109) (p = 0.011). No fusions were seen in oligodendrogliomas. The most frequently observed therapeutically targetable fusions were in FGFR (n = 12), MET (n = 11), and NTRK (n = 8). Several additional novel fusions that have not been previously described in gliomas were identified including EGFR:VWC2 and FGFR3:NBR1. In summary, targetable gene fusions are enriched in IDH wild-type high-grade astrocytic tumors, which will influence enrollment in and interpretation of clinical trials of glioma patients.
Medical Subject Headings
Adult; Astrocytes (pathology); Astrocytoma (genetics, pathology); Brain Neoplasms (genetics, pathology); Cell Lineage; Child; Female; Gene Fusion (genetics); Glioblastoma (genetics, pathology); Glioma (genetics, pathology); Humans; Isocitrate Dehydrogenase (genetics); Male; Mutation; Oligodendroglioma (genetics, pathology)
Journal of neuropathology and experimental neurology
Digital Object Identifier (DOI)
Ferguson, Sherise D.; Zhou, Shouhao; Huse, Jason T.; de Groot, John F.; Xiu, Joanne; Subramaniam, Deepa S.; Mehta, Shwetal; Gatalica, Zoran; Swensen, Jeffrey; Sanai, Nader; Spetzler, David; and Heimberger, Amy B., "Targetable Gene Fusions Associate With the IDH Wild-Type Astrocytic Lineage in Adult Gliomas" (2018). Translational Neuroscience. 1607.