Zheng, T;
Ghasemi, DR;
Okonechnikov, K;
Korshunov, A;
Sill, M;
Maass, KK;
Benites Goncalves da Silva, P;
... Pajtler, KW; + view all
(2021)
Cross-Species Genomics Reveals Oncogenic Dependencies in ZFTA/C11orf95 Fusion–Positive Supratentorial Ependymomas.
Cancer Discovery
, 11
(9)
pp. 2230-2247.
10.1158/2159-8290.CD-20-0963.
Preview |
Text
Brandner_PLAGL1_EPN.pdf - Accepted Version Download (1MB) | Preview |
Abstract
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.
Loading...
Loading...Loading...Loading...Archive Staff Only
 |
View Item |
