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

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 (RELA ^FUS ). Neural stem cells transduced with RELA ^FUS ex 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 RELA ^FUS 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 RELA ^FUS drives ST-ependymoma formation from periventricular neural stem cells in mice and that RELA ^FUS -induced tumorigenesis is likely dependent on a series of cell signaling pathways in addition to NF-κB.
(Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)