Central neurocytoma exhibits radial glial cell signatures with FGFR3 hypomethylation and overexpression

Exp Mol Med. 2024 Apr;56(4):975-986. doi: 10.1038/s12276-024-01204-3. Epub 2024 Apr 12.

Abstract

We explored the genomic events underlying central neurocytoma (CN), a rare neoplasm of the central nervous system, via multiomics approaches, including whole-exome sequencing, bulk and single-nuclei RNA sequencing, and methylation sequencing. We identified FGFR3 hypomethylation leading to FGFR3 overexpression as a major event in the ontogeny of CN that affects crucial downstream events, such as aberrant PI3K-AKT activity and neuronal development pathways. Furthermore, we found similarities between CN and radial glial cells based on analyses of gene markers and CN tumor cells and postulate that CN tumorigenesis is due to dysregulation of radial glial cell differentiation into neurons. Our data demonstrate the potential role of FGFR3 as one of the leading drivers of tumorigenesis in CN.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Methylation*
  • Ependymoglial Cells* / metabolism
  • Ependymoglial Cells* / pathology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neurocytoma* / genetics
  • Neurocytoma* / metabolism
  • Neurocytoma* / pathology
  • Receptor, Fibroblast Growth Factor, Type 3* / genetics
  • Receptor, Fibroblast Growth Factor, Type 3* / metabolism

Substances

  • Receptor, Fibroblast Growth Factor, Type 3
  • FGFR3 protein, human