ATRX In-Frame Fusion Neuroblastoma Is Sensitive to EZH2 Inhibition via Modulation of Neuronal Gene Signatures

Zulekha A. Qadeer, David Valle-Garcia, Dan Hasson, Zhen Sun, April Cook, Christie Nguyen, Aroa Soriano, Anqi Ma, Lyra M. Griffiths, Maged Zeineldin, Dan Filipescu, Luz Jubierre, Asif Chowdhury, Orla Deevy, Xiang Chen, David B. Finkelstein, Armita Bahrami, Elizabeth Stewart, Sara Federico, Soledad GallegoFumiko Dekio, Mary Fowkes, David Meni, John M. Maris, William A. Weiss, Stephen S. Roberts, Nai Kong V. Cheung, Jian Jin, Miguel F. Segura, Michael A. Dyer, Emily Bernstein

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Qadeer et al. show that ATRX in-frame fusions (IFF), found in a subset of neuroblastomas, are redistributed from wild-type ATRX-binding sites to other genomic regions, including the REST promoter. REST expression silences neuronal differentiation genes, which can be derepressed with EZH2 inhibitors to suppress ATRX IFF cell growth.

Original languageEnglish
Pages (from-to)512-527.e9
JournalCancer Cell
Volume36
Issue number5
DOIs
StatePublished - 11 Nov 2019

Keywords

  • ATRX
  • EZH2
  • REST
  • epigenetic therapeutics
  • neuroblastoma
  • neuronal differentiation
  • tazemetostat

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