TY - JOUR
AU - Zheng, Tuyu
AU - Ghasemi, David R
AU - Okonechnikov, Konstantin
AU - Korshunov, Andrey
AU - Sill, Martin
AU - Maass, Kendra K
AU - Benites Goncalves da Silva, Patricia
AU - Ryzhova, Marina
AU - Gojo, Johannes
AU - Stichel, Damian
AU - Arabzade, Amir
AU - Kupp, Robert
AU - Benzel, Julia
AU - Taya, Shinichiro
AU - Adachi, Toma
AU - Shiraishi, Ryo
AU - Gerber, Nicolas U
AU - Sturm, Dominik
AU - Ecker, Jonas
AU - Sievers, Philipp
AU - Selt, Florian
AU - Chapman, Rebecca
AU - Haberler, Christine
AU - Figarella-Branger, Dominique
AU - Reifenberger, Guido
AU - Fleischhack, Gudrun
AU - Rutkowski, Stefan
AU - Donson, Andrew M
AU - Ramaswamy, Vijay
AU - Capper, David
AU - Ellison, David W
AU - Herold-Mende, Christel C
AU - Schuller, Ulrich
AU - Brandner, Sebastian
AU - Hernaiz Driever, Pablo
AU - Kros, Johan M
AU - Snuderl, Matija
AU - Milde, Till
AU - Grundy, Richard G
AU - Hoshino, Mikio
AU - Mack, Stephen C
AU - Gilbertson, Richard J
AU - Jones, David T W
AU - Kool, Marcel
AU - von Deimling, Andreas
AU - Pfister, Stefan M
AU - Sahm, Felix
AU - Kawauchi, Daisuke
AU - Pajtler, Kristian
TI - Cross-species genomics reveals oncogenic dependencies in ZFTA/C11orf95 fusion-positive supratentorial ependymomas.
JO - Cancer discovery
VL - 11
IS - 9
SN - 2159-8290
CY - Philadelphia, Pa.
M1 - DKFZ-2021-00917
SP - 2230-2247
PY - 2021
N1 - #EA:B062#LA:B062#B300# /2021 Sep;11(9):2230-2247
AB - 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.
LB - PUB:(DE-HGF)16
C6 - pmid:33879448
DO - DOI:10.1158/2159-8290.CD-20-0963
UR - https://inrepo02.dkfz.de/record/168443
ER -