A De Novo Mouse Model of C11orf95-RELA Fusion-Driven Ependymoma Identifies Driver Functions in Addition to NF-κB

Cell Rep. 2018 Jun 26;23(13):3787-3797. doi: 10.1016/j.celrep.2018.04.099.

Abstract

The majority of supratentorial ependymomas (ST-ependymomas) have few mutations but frequently display chromothripsis of chromosome 11q that generates a fusion between C11orf95 and RELA (RELAFUS). Neural stem cells transduced with RELAFUSex vivo form ependymomas when implanted in the brain. These tumors display enhanced NF-κB signaling, suggesting that this aberrant signal is the principal mechanism of oncogenesis. However, it is not known whether RELAFUS is sufficient to drive de novo ependymoma tumorigenesis in the brain and, if so, whether these tumors also arise from neural stem cells. We show that RELAFUS drives ST-ependymoma formation from periventricular neural stem cells in mice and that RELAFUS-induced tumorigenesis is likely dependent on a series of cell signaling pathways in addition to NF-κB.

Keywords: C11orf95; NF-κB signaling; RCAS/tv-a system; RELA; ependymoma; fusion gene; mouse model.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Cell Transformation, Neoplastic
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Disease Models, Animal
  • Ependymoma / genetics
  • Ependymoma / metabolism
  • Ependymoma / pathology
  • Mice
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism
  • Oncogene Fusion
  • Principal Component Analysis
  • Signal Transduction
  • Transcription Factor RelA / genetics*
  • Transcription Factor RelA / metabolism
  • Transcriptome

Substances

  • 2700081O15Rik protein, mouse
  • DNA-Binding Proteins
  • Transcription Factor RelA