| Title: |
Cross-Species Genomics Reveals Oncogenic Dependencies in ZFTA/C11orf95 Fusion–Positive Supratentorial Ependymomas |
| Authors: |
Zheng, T; Ghasemi, DR; Okonechnikov, K; Korshunov, A; Sill, M; Maass, KK; Benites Goncalves da Silva, P; Ryzhova, M; Gojo, J; Stichel, D; Arabzade, A; Kupp, R; Benzel, J; Taya, S; Adachi, T; Shiraishi, R; Gerber, NU; Sturm, D; Ecker, J; Sievers, P; Selt, F; Chapman, R; Haberler, C; Figarella-Branger, D; Reifenberger, G; Fleischhack, G; Rutkowski, S; Donson, AM; Ramaswamy, V; Capper, D; Ellison, DW; Herold-Mende, CC; Schuller, U; Brandner, S; Hernaiz Driever, P; Kros, JM; Snuderl, M; Milde, T; Grundy, RG; Hoshino, M; Mack, SC; Gilbertson, RJ; Jones, DTW; Kool, M; von Deimling, A; Pfister, SM; Sahm, F; Kawauchi, D; Pajtler, KW |
| Source: |
Cancer Discovery , 11 (9) pp. 2230-2247. (2021) |
| Publication Year: |
2021 |
| Collection: |
University College London: UCL Discovery |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
text |
| Language: |
English |
| Relation: |
https://discovery.ucl.ac.uk/id/eprint/10128589/1/Brandner_PLAGL1_EPN.pdf; https://discovery.ucl.ac.uk/id/eprint/10128589/ |
| Availability: |
https://discovery.ucl.ac.uk/id/eprint/10128589/1/Brandner_PLAGL1_EPN.pdf; https://discovery.ucl.ac.uk/id/eprint/10128589/ |
| Rights: |
open |
| Accession Number: |
edsbas.9D3BEFC6 |
| Database: |
BASE |