%0 Journal Article
%A Zheng, Tuyu
%A Ghasemi, David R
%A Okonechnikov, Konstantin
%A Korshunov, Andrey
%A Sill, Martin
%A Maass, Kendra K
%A Benites Goncalves da Silva, Patricia
%A Ryzhova, Marina
%A Gojo, Johannes
%A Stichel, Damian
%A Arabzade, Amir
%A Kupp, Robert
%A Benzel, Julia
%A Taya, Shinichiro
%A Adachi, Toma
%A Shiraishi, Ryo
%A Gerber, Nicolas U
%A Sturm, Dominik
%A Ecker, Jonas
%A Sievers, Philipp
%A Selt, Florian
%A Chapman, Rebecca
%A Haberler, Christine
%A Figarella-Branger, Dominique
%A Reifenberger, Guido
%A Fleischhack, Gudrun
%A Rutkowski, Stefan
%A Donson, Andrew M
%A Ramaswamy, Vijay
%A Capper, David
%A Ellison, David W
%A Herold-Mende, Christel C
%A Schuller, Ulrich
%A Brandner, Sebastian
%A Hernaiz Driever, Pablo
%A Kros, Johan M
%A Snuderl, Matija
%A Milde, Till
%A Grundy, Richard G
%A Hoshino, Mikio
%A Mack, Stephen C
%A Gilbertson, Richard J
%A Jones, David T W
%A Kool, Marcel
%A von Deimling, Andreas
%A Pfister, Stefan M
%A Sahm, Felix
%A Kawauchi, Daisuke
%A Pajtler, Kristian
%T Cross-species genomics reveals oncogenic dependencies in ZFTA/C11orf95 fusion-positive supratentorial ependymomas.
%J Cancer discovery
%V 11
%N 9
%@ 2159-8290
%C Philadelphia, Pa.
%M DKFZ-2021-00917
%P 2230-2247
%D 2021
%Z #EA:B062#LA:B062#B300# /2021 Sep;11(9):2230-2247
%X Molecular groups of supratentorial ependymomas comprise tumors with ZFTA-RELA or YAP1-involving fusions and fusion-negative subependymoma. However, occasionally supratentorial ependymomas cannot be readily assigned to any of these groups due to lack of detection of a typical fusion and/or ambiguous DNA methylation-based classification. An unbiased approach with a cohort of unprecedented size revealed distinct methylation clusters composed of tumors with ependymal but also various other histological features containing alternative translocations that shared ZFTA as a partner gene. Somatic overexpression of ZFTA-associated fusion genes in the developing cerebral cortex is capable of inducing tumor formation in vivo, and cross-species comparative analyses identified GLI2 as a key downstream regulator of tumorigenesis in all tumors. Targeting GLI2 with arsenic trioxide caused extended survival of tumor-bearing animals, indicating a potential therapeutic vulnerability in ZFTA fusion-positive tumors.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:33879448
%R 10.1158/2159-8290.CD-20-0963
%U https://inrepo02.dkfz.de/record/168443