Diffuse midline glioma with novel, potentially targetable, FGFR2-VPS35 fusion

Cold Spring Harb Mol Case Stud. 2020 Oct 7;6(5):a005660. doi: 10.1101/mcs.a005660. Print 2020 Oct.

Abstract

We report a case of a slow-growing, diffuse, infiltrating glioma in the right brainstem of a 9-yr-old boy. The tumor was negative by immunohistochemical staining for histone H3 K27M, BRAF V600E, and IDH1 R132H mutations. Fluorescence in situ hybridization did not reveal a BRAF duplication. Genomic profiling of the tumor, by DNA methylation array and cancer whole-exome and transcriptome sequencing, was performed. This analysis showed copy-number alterations, including gains of several chromosomes. In addition, a novel fusion involving the first 17 exons of FGFR2 fused to exon 2 of VPS35 was identified. This novel fusion is predicted to result in activation of fibroblast growth factor receptor (FGFR) signaling and is potentially targetable using FGFR inhibitors. This tumor expands the spectrum of pediatric diffuse gliomas.

Keywords: neoplasm of the central nervous system.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Neoplasms / genetics
  • Child
  • Exome Sequencing / methods
  • Glioma / genetics*
  • Humans
  • In Situ Hybridization, Fluorescence / methods
  • Male
  • Mutation / genetics
  • Receptor, Fibroblast Growth Factor, Type 2 / genetics*
  • Vesicular Transport Proteins / genetics*

Substances

  • VPS35 protein, human
  • Vesicular Transport Proteins
  • FGFR2 protein, human
  • Receptor, Fibroblast Growth Factor, Type 2