A de novo mouse model of C11orf95-RELA fusion-driven ependymoma identifies driver functions in addition to NFκB

The vast majority of supratentorial ependymomas (ST-EPNs) have few mutations other than chromosomal rearrangements on chromosome 11, most generating a fusion between C11orf95 and RELA (CR). This CR fusion can transform stem cells ex vivo rendering them oncogenic and may possess NF-κB activity, which has been proposed to be a mechanism of oncogenesis. However, it is not known whether CR is sufficient for EPN formation in vivo, and from what cell type and location. We found that CR is sufficient to form tumors from cells in the ependymal zone in mice that show many molecular and histologic similarities to human ST-EPN. Furthermore, the activation of NF-κB by this fusion protein appears minimal and not related to its oncogenic activity C11orf95-RELA is a potent oncogene for supratentorial ependymoma