Journal Article

DKFZ-2021-00679

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png ZFTA-RELA Dictates Oncogenic Transcriptional Programs to Drive Aggressive Supratentorial Ependymoma.

Arabzade, A. ; Zhao, Y. ; Varadharajan, S. ; Chen, H.-C. ; Jessa, S. ; Rivas, B. ; Stuckert, A. J. ; Solis, M. ; Kardian, A. ; Tlais, D. ; Golbourn, B. J. ; Stanton, A. J. ; Chan, Y. S. ; Olson, C. ; Karlin, K. L. ; Kong, K. ; Kupp, R. ; Hu, B. ; Injac, S. G. ; Ngo, M. ; Wang, P. R. ; De Leon, L. A. ; Sahm, F.DKFZ* ; Kawauchi, D.DKFZ* ; Pfister, S.DKFZ* ; Lin, C. Y. ; Hodges, H. C. ; Singh, I. ; Westbrook, T. F. ; Chintagumpala, M. M. ; Blaney, S. M. ; Parsons, D. W. ; Pajtler, K. W.DKFZ* ; Agnihotri, S. ; Gilbertson, R. J. ; Yi, J. ; Jabado, N. ; Kleinman, C. L. ; Bertrand, K. C. ; Deneen, B. ; Mack, S. C.

2021
Philadelphia, Pa.

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Please use a persistent id in citations: doi:10.1158/2159-8290.CD-20-1066

Abstract: Over 60% of supratentorial (ST) ependymomas harbor a ZFTA-RELA (ZRfus) gene fusion (formerly C11orf95-RELA). To study the biology of ZRfus, we developed an autochthonous mouse tumor model using in utero electroporation (IUE) of the embryonic mouse brain. Integrative epigenomic and transcriptomic mapping was performed on IUE driven ZRfus tumors by CUT&RUN, ChIP, ATAC, and RNA sequencing and compared to human ZRfus driven ependymoma. In addition to direct canonical NF-kB pathway activation, ZRfus dictates a neoplastic transcriptional program and binds to thousands of unique sites across the genome that are enriched with Plagl family transcription factor (TF) motifs. ZRfus activates gene expression programs through recruitment of transcriptional co-activators (Brd4, Ep300, Cbp, Pol2) that are amenable to pharmacologic inhibition. Downstream ZRfus target genes converge on developmental programs marked by Plagl transcription factor proteins, and activate neoplastic programs enriched in Mapk, focal adhesion, and gene imprinting networks.

Note: 2021 Sep;11(9):2200-2215

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Contributing Institute(s):

1. B062 Pädiatrische Neuroonkologie (B062)
2. DKTK HD zentral (HD01)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2021

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Essential Science Indicators ; IF >= 25 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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