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 Gallego; Fumiko 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

doi:10.1016/j.ccell.2019.09.002

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 journal › Article › peer-review

15 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 language	English (US)
Pages (from-to)	512-527.e9
Journal	Cancer cell
Volume	36
Issue number	5
DOIs	https://doi.org/10.1016/j.ccell.2019.09.002
State	Published - Nov 11 2019
Externally published	Yes

Keywords

ATRX
EZH2
REST
epigenetic therapeutics
neuroblastoma
neuronal differentiation
tazemetostat

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1016/j.ccell.2019.09.002

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Qadeer, Z. A., Valle-Garcia, D., Hasson, D., Sun, Z., Cook, A., Nguyen, C., Soriano, A., Ma, A., Griffiths, L. M., Zeineldin, M., Filipescu, D., Jubierre, L., Chowdhury, A., Deevy, O., Chen, X., Finkelstein, D. B., Bahrami, A., Stewart, E., Federico, S., ... Bernstein, E. (2019). ATRX In-Frame Fusion Neuroblastoma Is Sensitive to EZH2 Inhibition via Modulation of Neuronal Gene Signatures. Cancer cell, 36(5), 512-527.e9. https://doi.org/10.1016/j.ccell.2019.09.002

Qadeer, ZA, Valle-Garcia, D, Hasson, D, Sun, Z, Cook, A, Nguyen, C, Soriano, A, Ma, A, Griffiths, LM, Zeineldin, M, Filipescu, D, Jubierre, L, Chowdhury, A, Deevy, O, Chen, X, Finkelstein, DB, Bahrami, A, Stewart, E, Federico, S, Gallego, S, Dekio, F, Fowkes, M, Meni, D, Maris, JM, Weiss, WA, Roberts, SS, Cheung, NKV, Jin, J, Segura, MF, Dyer, MA & Bernstein, E 2019, 'ATRX In-Frame Fusion Neuroblastoma Is Sensitive to EZH2 Inhibition via Modulation of Neuronal Gene Signatures', Cancer cell, vol. 36, no. 5, pp. 512-527.e9. https://doi.org/10.1016/j.ccell.2019.09.002

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

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.",

keywords = "ATRX, EZH2, REST, epigenetic therapeutics, neuroblastoma, neuronal differentiation, tazemetostat",

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

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year = "2019",

month = nov,

day = "11",

doi = "10.1016/j.ccell.2019.09.002",

language = "English (US)",

volume = "36",

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AU - Qadeer, Zulekha A.

AU - Valle-Garcia, David

AU - Hasson, Dan

AU - Sun, Zhen

AU - Cook, April

AU - Nguyen, Christie

AU - Soriano, Aroa

AU - Ma, Anqi

AU - Griffiths, Lyra M.

AU - Zeineldin, Maged

AU - Filipescu, Dan

AU - Jubierre, Luz

AU - Chowdhury, Asif

AU - Deevy, Orla

AU - Chen, Xiang

AU - Finkelstein, David B.

AU - Bahrami, Armita

AU - Stewart, Elizabeth

AU - Federico, Sara

AU - Gallego, Soledad

AU - Dekio, Fumiko

AU - Fowkes, Mary

AU - Meni, David

AU - Maris, John M.

AU - Weiss, William A.

AU - Roberts, Stephen S.

AU - Cheung, Nai Kong V.

AU - Jin, Jian

AU - Segura, Miguel F.

AU - Dyer, Michael A.

AU - Bernstein, Emily

PY - 2019/11/11

Y1 - 2019/11/11

N2 - 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.

AB - 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.

KW - ATRX

KW - EZH2

KW - REST

KW - epigenetic therapeutics

KW - neuroblastoma

KW - neuronal differentiation

KW - tazemetostat

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M3 - Article

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AN - SCOPUS:85074426501

SN - 1535-6108

VL - 36

SP - 512-527.e9

JO - Cancer cell

JF - Cancer cell

IS - 5

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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