%0 Journal Article
%A Pajtler, Kristian
%A Wei, Yiju
%A Okonechnikov, Konstantin
%A Silva, Patricia B G
%A Vouri, Mikaella
%A Zhang, Lei
%A Brabetz, Sebastian
%A Sieber, Laura
%A Gulley, Melissa
%A Mauermann, Monika
%A Wedig, Tatjana
%A Mack, Norman
%A Imamura Kawasawa, Yuka
%A Sharma, Tanvi
%A Zuckermann, Marc
%A Andreiuolo, Felipe
%A Holland, Eric
%A Maass, Kendra
%A Körkel-Qu, Huiqin
%A Liu, Hai-Kun
%A Sahm, Felix
%A Capper, David
%A Bunt, Jens
%A Richards, Linda J
%A Jones, David T W
%A Korshunov, Andrey
%A Chavez, Lukas
%A Lichter, Peter
%A Hoshino, Mikio
%A Pfister, Stefan
%A Kool, Marcel
%A Li, Wei
%A Kawauchi, Daisuke
%T YAP1 subgroup supratentorial ependymoma requires TEAD and nuclear factor I-mediated transcriptional programmes for tumorigenesis.
%J Nature Communications
%V 10
%N 1
%@ 2041-1723
%C [London]
%I Nature Publishing Group UK
%M DKFZ-2019-02201
%P 3914
%D 2019
%X YAP1 fusion-positive supratentorial ependymomas predominantly occur in infants, but the molecular mechanisms of oncogenesis are unknown. Here we show YAP1-MAMLD1 fusions are sufficient to drive malignant transformation in mice, and the resulting tumors share histo-molecular characteristics of human ependymomas. Nuclear localization of YAP1-MAMLD1 protein is mediated by MAMLD1 and independent of YAP1-Ser127 phosphorylation. Chromatin immunoprecipitation-sequencing analyses of human YAP1-MAMLD1-positive ependymoma reveal enrichment of NFI and TEAD transcription factor binding site motifs in YAP1-bound regulatory elements, suggesting a role for these transcription factors in YAP1-MAMLD1-driven tumorigenesis. Mutation of the TEAD binding site in the YAP1 fusion or repression of NFI targets prevents tumor induction in mice. Together, these results demonstrate that the YAP1-MAMLD1 fusion functions as an oncogenic driver of ependymoma through recruitment of TEADs and NFIs, indicating a rationale for preclinical studies to block the interaction between YAP1 fusions and NFI and TEAD transcription factors.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:31477715
%2 pmc:PMC6718408
%R 10.1038/s41467-019-11884-5
%U https://inrepo02.dkfz.de/record/144769