Targetable Gene Fusions Associate With the IDH Wild-Type Astrocytic Lineage in Adult Gliomas

J Neuropathol Exp Neurol. 2018 Jun 1;77(6):437-442. doi: 10.1093/jnen/nly022.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Astrocytes / pathology*
  • Astrocytoma / genetics*
  • Astrocytoma / pathology*
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology*
  • Cell Lineage
  • Child
  • Female
  • Gene Fusion / genetics*
  • Glioblastoma / genetics
  • Glioblastoma / pathology
  • Glioma / genetics*
  • Glioma / pathology*
  • Humans
  • Isocitrate Dehydrogenase / genetics*
  • Male
  • Mutation
  • Oligodendroglioma / genetics
  • Oligodendroglioma / pathology

Substances

  • Isocitrate Dehydrogenase