ArticleCancer cell2019
ATRX In-Frame Fusion Neuroblastoma Is Sensitive to EZH2 Inhibition via Modulation of Neuronal Gene Signatures.
Registry-linked trialOpen access · bronzeAbstract read
In one paragraph
Article in Cancer cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06502210 (Identification of New Gene Spliceosomes in Neuroblastoma and Their Translational Application in Clinical Accurate Diagnosis and Therapy), which is not on this map. Cited by 48 papers.
0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
3.8field-weighted citation impact, top 6% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Identification of New Gene Spliceosomes in Neuroblastoma and Their Translational Application in Clinical Accurate Diagnosis and Therapy
Who cites it
48 citing papers in PubMed, 116 citations in OpenAlex.
- 5-hydroxymethylcytosine deposition mediates Polycomb repressive complex 2 function iniScience · 2026Article
- COLEC12 promotes pancreatic cancer progression via the activation of the TGF-β signaling pathway.Molecular and cellular biochemistry · 2026Article
- Mutant Huntingtin disrupts neurogenic and astroglial programs via the EZH2-Let-7g-LIN28 axis with rescue by epigenetic modulators.Cell death and differentiation · 2026Article
- Inhibition of USP7 Destabilizes the Noncanonical PRC1.1 Complex and Induces Neuroblastoma Differentiation.Molecular cancer research : MCR · 2026Article
- Frequency and Prognostic Significance of Genetic Abnormalities in a Subgroup of Patients With Intermediate-Risk Neuroblastoma: A SIOPEN Study.JCO precision oncology · 2026Article
- The landscape of structural variation in pediatric cancer.Cancer cell · 2026Article
- Human stem cell models for group 3 medulloblastoma uncover JARID1B as a regulator of the chromatin landscape.bioRxiv : the preprint server for biology · 2025Article
- Noncanonical PRC1.1 targets BTG2 to retain cyclin gene expression and cell growth in neuroblastoma.Oncogenesis · 2025Article
- Peripheral neuroblastic tumors behaving badly: an update on high-risk morphologic and molecular groupings.Virchows Archiv : an international journal of pathology · 2025Review
- Longitudinal single-cell multiomic atlas of high-risk neuroblastoma reveals chemotherapy-induced tumor microenvironment rewiring.Nature genetics · 2025Article
- The landscape of structural variation in pediatric cancer.bioRxiv : the preprint server for biology · 2025Article
- ATRX mutations mediate an immunogenic phenotype and macrophage infiltration in neuroblastoma.Cancer letters · 2025Article
- PRELP inhibits colorectal cancer progression by suppressing epithelial-mesenchymal transition and angiogenesis via the inactivation of the FGF1/PI3K/AKT pathway.Apoptosis : an international journal on programmed cell death · 2025Article
- The TERT Promoter is Polycomb-Repressed in Neuroblastoma Cells with Long Telomeres.Cancer research communications · 2024Article
- Androgen deprivation induces neuroendocrine phenotypes in prostate cancer cells through CREB1/EZH2-mediated downregulation of REST.Cell death discovery · 2024Article
- Gut microbiota-derived butyrate restores impaired regulatory T cells in patients with AChR myasthenia gravis via mTOR-mediated autophagy.Cell communication and signaling : CCS · 2024Article
- Mutant ATRX: pathogenesis of ATRX syndrome and cancer.Frontiers in molecular biosciences · 2024Review
- Targeting the ubiquitin-proteasome system: a novel therapeutic strategy for neuroblastoma.Frontiers in oncology · 2024Review
- Telomere Maintenance Mechanisms in a Cohort of High-Risk Neuroblastoma Tumors and Its Relation to Genomic Variants in theCancers · 2023Article
- Androgen deprivation induces neuroendocrine phenotypes in prostate cancer cells through CREB1/EZH2-mediated downregulation of REST.Research square · 2023Article
Corrections and comments
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Authors and funding
31 authors at 7 institutions in 2 countries.
Zulekha A QadeerDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Departments of Neurology, Neurosurgery, and Pediatrics, University of California, San Francisco, San Francisco, CA 94158, USA.
David Valle-GarciaDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Dan HassonDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Zhen SunDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
April CookDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Christie NguyenDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Aroa SorianoLaboratory of Translational Research in Child and Adolescent Cancer, Vall d'Hebron Institut de Recerca (VHIR), Barcelona 08035, Spain.
Anqi MaDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Lyra M GriffithsDepartment of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Maged ZeineldinDepartment of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Dan FilipescuDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Luz JubierreLaboratory of Translational Research in Child and Adolescent Cancer, Vall d'Hebron Institut de Recerca (VHIR), Barcelona 08035, Spain.
Asif ChowdhuryDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Orla DeevyDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Xiang ChenDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
David B FinkelsteinDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Armita BahramiDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Elizabeth StewartDepartment of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Sara FedericoDepartment of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Soledad GallegoPediatric Oncology and Hematology Department, University Hospital Vall d'Hebron, Barcelona 08035, Spain.
Fumiko DekioDepartment of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Mary FowkesDepartment of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
David MeniDepartment of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
John M MarisCenter for Childhood Cancer Research at the Children's Hospital of Philadelphia, Perlman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
William A WeissDepartments of Neurology, Neurosurgery, and Pediatrics, University of California, San Francisco, San Francisco, CA 94158, USA.
Stephen S RobertsDepartment of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Nai-Kong V CheungDepartment of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Jian JinDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Miguel F SeguraLaboratory of Translational Research in Child and Adolescent Cancer, Vall d'Hebron Institut de Recerca (VHIR), Barcelona 08035, Spain.
Michael A DyerDepartment of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Emily BernsteinDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: emily.bernstein@mssm.edu.
Icahn School of Medicine at Mount Sinai · USSt. Jude Children's Research Hospital · USMemorial Sloan Kettering Cancer Center · USVall d'Hebron Institut de Recerca · ESUniversity of California, San Francisco · USUniversity of Pennsylvania · USVall d'Hebron Hospital Universitari · ES
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4MViral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI CHARLES ROBERTS · 1985 to 2026
$166.9MTHE TISCH CANCER INSTITUTE - CANCER CENTER SUPPORT GRANTP30CA196521 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Deanna L Benson · 2015 to 2026
$35.4MTRAINING PROGRAM IN CANCER THERAPYT32CA078207 · NCI · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI James J Manfredi · 1999 to 2026
$11.6MDiscovering mechanisms of neuroblastoma tumorigenesis to improve patient outcomesR35CA220500 · NCI · CHILDREN'S HOSP OF PHILADELPHIA · PI JOHN M MARIS · 2017 to 2026
$8.7MTraining Program in Translational Brain Tumor ResearchT32CA151022 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Joseph F Costello · 2010 to 2026
$6.6MThe Genetic Basis of Neuroblastoma TumorigenesisR01CA124709 · NCI · CHILDREN'S HOSP OF PHILADELPHIA · PI MARIS, JOHN M · 2008 to 2017
$6.3MProliferation Control in the Retina: The Rb FamilyR01EY014867 · NEI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI DYER, MICHAEL A · 2003 to 2012
$4.5MProliferation and Differentiation of Retinal Stem CellsR01EY018599 · NEI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI DYER, MICHAEL A · 2008 to 2011
$2.5MMechanisms and Modeling of Neuroblastoma-Associated ATRX AlterationsR01NS110837 · NINDS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI BERNSTEIN, EMILY · 2020 to 2024
$2.0MTransforming Genomics with 5 PB Big Omics Data Engine Cray CS300-AC SupercomputerS10OD018522 · OD · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI KOVATCH, PATRICIA · 2014 to 2014
$1.9MMolecular Targeted Therapy for RetinoblastomaR01CA168875 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI DYER, MICHAEL A · 2012 to 2016
$1.8MNCI NIH HHS P30 CA008748NCI NIH HHS P30 CA021765NCI NIH HHS P30 CA196521NCI NIH HHS R01 CA124709NCI NIH HHS R01 CA168875NCI NIH HHS R35 CA220500NCI NIH HHS T32 CA078207NCI NIH HHS T32 CA151022NEI NIH HHS R01 EY014867NEI NIH HHS R01 EY018599NIGMS NIH HHS R01 GM122749NIH HHS S10 OD018522NINDS NIH HHS R01 NS110837
Abstract
ATRX alterations occur at high frequency in neuroblastoma of adolescents and young adults. Particularly intriguing are the large N-terminal deletions of ATRX (Alpha Thalassemia/Mental Retardation, X-linked) that generate in-frame fusion (IFF) proteins devoid of key chromatin interaction domains, while retaining the SWI/SNF-like helicase region. We demonstrate that ATRX IFF proteins are redistributed from H3K9me3-enriched chromatin to promoters of active genes and identify REST as an ATRX IFF target whose activation promotes silencing of neuronal differentiation genes. We further show that ATRX IFF cells display sensitivity to EZH2 inhibitors, due to derepression of neurogenesis genes, including a subset of REST targets. Taken together, we demonstrate that ATRX structural alterations are not loss-of-function and put forward EZH2 inhibitors as a potential therapy for ATRX IFF neuroblastoma.
Indexed as
Gene Expression Regulation, NeoplasticAnimalsBase SequenceCell DifferentiationCell Line, TumorChromatinEnhancer of Zeste Homolog 2 ProteinEpigenesis, GeneticFemaleHistonesHumansMaleMiceNeuroblastomaNeurogenesisNeuronsATRX protein, humanChromatinEnhancer of Zeste Homolog 2 ProteinEZH2 protein, humanHistonesRE1-Silencing Transcription FactorRepressor ProteinsX-linked Nuclear ProteinATRXepigenetic therapeuticsEZH2neuroblastomaneuronal differentiationRESTtazemetostat
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Registered trials
NCT06502210ClinicalTrials.gov
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.