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

Publication date: 26 June 2018
Source:Cell Reports, Volume 23, Issue 13
Author(s): Tatsuya Ozawa, Sonali Arora, Frank Szulzewsky, Gordana Juric-Sekhar, Yoshiteru Miyajima, Hamid Bolouri, Yoshie Yasui, Jason Barber, Robert Kupp, James Dalton, Terreia S. Jones, Mitsutoshi Nakada, Toshihiro Kumabe, David W. Ellison, Richard J. Gilbertson, Eric C. Holland
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^FUSex 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.

Graphical abstract

Teaser

The C11orf95-RELA fusion (RELA^FUS) has been found in a distinct subset of supratentorial ependymomas. Ozawa et al. show that RELA^FUS is sufficient to drive ST-ependymoma formation from periventricular neural stem cells in mice. Furthermore, they show that RELA^FUS-induced tumorigenesis might depend on other cell signaling pathways in addition to NF-κB.


https://ift.tt/2Kk73To