ArticleScience translational medicine2016
ATRX loss promotes tumor growth and impairs nonhomologous end joining DNA repair in glioma.
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Article in Science translational medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 195 papers, 1 of them a synthesis that pooled it.
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195citing papers in PubMed, 1 pooled it
16.9field-weighted citation impact, top 1% of its field
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Who cites it
195 citing papers in PubMed, 1 synthesis or guideline pooled it, 298 citations in OpenAlex.
- The diagnostic and prediction performance of MR diffusion kurtosis imaging in the glioma molecular classification: a systematic review and meta-analysis.Frontiers in neurology · 2025Pooled it
- Trial
- Autophagy inhibition sensitizes radiotherapy responses in high-grade mutant IDH1 glioma.Nature communications · 2026Article
- ATRX Condensates as Candidate Organizers of Enhancer-Centered Nuclear Microenvironments in Neural Progenitors: A Hypothesis for Enhancer-Associated ATRX Function in Neural Progenitors.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- A dual pronged approach to cancer immune exclusion: tumor-derived LAIR-1 simultaneously drives fibrosis and blocks immune recruitment in glioma.Research square · 2026Article
- Translational control by RPL22L1-specific ribosomes enhances DNA repair and chemoresistance.Nature communications · 2026Article
- The impact of international care networks on the clinical management of constitutional mismatch repair deficiency (CMMRD): a review of recent developments.Familial cancer · 2026Review
- ATRX inactivation disrupts global chromatin state and topology to dysregulate neurodevelopmental pathways in glioma pathogenesis.Nucleic acids research · 2026Article
- Brain Cancer: Molecular Alterations and Emerging Trends in Neuropharmacology.International journal of molecular sciences · 2026Review
- Astrocytes in neuroinflammation and brain cancer.Molecular biomedicine · 2026Review
- Explainable incremental-value analysis of apparent diffusion coefficient and arterial spin labeling radiomics for ATRX status prediction in glioblastoma.Frontiers in oncology · 2026Article
- High-grade astrocytoma with piloid features: a case report of comprehensive management.Frontiers in oncology · 2026Article
- Telomere-metabolism-immunity axis in sarcoma: Immune evasion mechanisms and therapeutic strategies.Clinical and translational medicine · 2025Review
- Flexynesis: A deep learning toolkit for bulk multi-omics data integration for precision oncology and beyond.Nature communications · 2025Article
- Autophagy Upregulation in Mutant Isocitrate Dehydrogenase 1 (IDH1) Glioma Uncovers a Novel Therapeutic Target.Research square · 2025Article
- Telomere Maintenance and DNA Repair: A Bidirectional Relationship in Cancer Biology and Therapy.Cancers · 2025Review
- Current Landscape of Preclinical Models for Pediatric Gliomas: Clinical Implications and Future Directions.Cancers · 2025Review
- Epigenetic reprogramming induced by key metabolite depletion is an evolutionarily ancient path to tumorigenesis.Disease models & mechanisms · 2025Article
- Blood-oxygenation-level-dependent (BOLD) MRI responses to COMagnetic resonance imaging · 2025Article
- Combined inhibition of de novo glutathione and nucleotide biosynthesis is synthetically lethal in glioblastoma.Cell reports · 2025Article
135 more citing papers are in PubMed but not listed here.
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Authors and funding
24 authors at 3 institutions in 1 country.
Carl KoschmannDivision of Pediatric Hematology-Oncology, Department of Pediatrics, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA. Departments of Neurosurgery and Cell and Developmental Biology, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.
Anda-Alexandra CalinescuDepartments of Neurosurgery and Cell and Developmental Biology, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.
Felipe J NunezDepartments of Neurosurgery and Cell and Developmental Biology, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.
Alan MackayDivisions of Molecular Pathology and Cancer Therapeutics, Institute of Cancer Research, London SM2 5NG, UK.
Janet Fazal-SalomDivisions of Molecular Pathology and Cancer Therapeutics, Institute of Cancer Research, London SM2 5NG, UK.
Daniel ThomasDepartments of Neurosurgery and Cell and Developmental Biology, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.
Flor MendezDepartments of Neurosurgery and Cell and Developmental Biology, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.
Neha KamranDepartments of Neurosurgery and Cell and Developmental Biology, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.
Marta DzamanDepartments of Neurosurgery and Cell and Developmental Biology, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.
Lakshman MulpuriDepartments of Neurosurgery and Cell and Developmental Biology, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.
Johnathon KrasinkiewiczDepartments of Neurosurgery and Cell and Developmental Biology, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.
Robert DohertyDepartments of Neurosurgery and Cell and Developmental Biology, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.
Rosemary LemonsDepartments of Neurosurgery and Cell and Developmental Biology, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.
Jacqueline A Brosnan-CashmanDepartment of Pathology, Johns Hopkins University, Baltimore, MD 21287, USA.
Youping LiDepartments of Neurosurgery and Cell and Developmental Biology, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.
Soyeon RohDepartments of Neurosurgery and Cell and Developmental Biology, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.
Lili ZhaoDepartment of Biostatistics, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.
Henry AppelmanDepartment of Pathology, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.
David FergusonDepartment of Pathology, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.
Vera GorbunovaDepartment of Biology, University of Rochester, Rochester, NY 14627, USA.
Alan MeekerDepartments of Pathology and Urology, Johns Hopkins University, Baltimore, MD 21287, USA.
Chris JonesDivisions of Molecular Pathology and Cancer Therapeutics, Institute of Cancer Research, London SM2 5NG, UK.
Pedro R LowensteinDepartments of Neurosurgery and Cell and Developmental Biology, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.
Maria G CastroDepartments of Neurosurgery and Cell and Developmental Biology, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA. mariacas@med.umich.edu.
University of Michigan–Ann Arbor · USJohns Hopkins University · USUniversity of Rochester · US
Funding
XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Alexey I Nesvizhskii · 1988 to 2026
$178.2MMichigan Institute for Clinical and Health Research (MICHR)UL1TR002240 · NCATS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LUMENG, JULIE C, MASHOUR, GEORGE ALEXANDER · 2017 to 2022
$54.9MMichigan Institute for Clinical and Health Research (MCHR)UL1TR000433 · NCATS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MASHOUR, GEORGE ALEXANDER · 2012 to 2016
$49.9MThe role of hyaluronan in longevity and cancer resistance of longest-lived rodentP01AG047200 · NIA · UNIVERSITY OF ROCHESTER · PI Andrei Seluanov · 2014 to 2026
$36.9MTRAINING IN AREAS FUNDAMENTAL TO CANCER RESEARCHT32CA009110 · NCI · JOHNS HOPKINS UNIVERSITY · PI MATUNIS, MICHAEL J., WEERARATNA, ASHANI T · 1985 to 2025
$13.1MTRAINING IN CLINICAL AND BASIC NEUROSCIENCET32NS007222 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Henry L Paulson · 1985 to 2026
$8.0MThe role of SIRT6 posttranslational modifications in aging and genome stability. Supplement: Testing SIRT6 activators as potential Alzheimer's disease therapy.R01AG027237 · NIA · UNIVERSITY OF ROCHESTER · PI Vera Gorbunova · 2006 to 2026
$6.2MUniversity of Michigan Postbaccalaureate Research Education Program (UM PREP)R25GM086262 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ALLEN, BENJAMIN · 2009 to 2024
$6.1MOligodendrocyte-focused rAAV gene therapy strategies for Canavan disease and LeukodystrophiesR01NS076991 · NINDS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Guangping Gao · 2012 to 2026
$5.7MGutless Adenovirus Mediated Gene Therapy for GliomaU01NS052465 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CASTRO, MARIA G · 2007 to 2011
$3.1MImmune-suppressive Myeloid Cells in the Glioma Microenvironment: Signaling Mechanisms and Novel Therapeutic StrategiesR37NS094804 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CASTRO, MARIA G · 2015 to 2021
$2.9MNeuroimmunology of Malignant Brain Tumors: Innate MechanismsR01NS096756 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LOWENSTEIN, PEDRO R. · 2016 to 2020
$2.1MNCATS NIH HHS UL1 TR000433NCATS NIH HHS UL1 TR002240NCI NIH HHS P30 CA046592NCI NIH HHS R01 CA172380NCI NIH HHS R01CA172380NCI NIH HHS T32 CA009110NIA NIH HHS P01 AG047200NIA NIH HHS R01 AG027237NIGMS NIH HHS R25 GM086262NIH HHS S10 OD020053NINDS NIH HHS 1R01-NS 054193NINDS NIH HHS 1R01-NS 057711NINDS NIH HHS 1R01-NS 061107NINDS NIH HHS 1R01-NS074387NINDS NIH HHS 1R01-NS082311NINDS NIH HHS 1U01-NS052465NINDS NIH HHS R01 NS054193NINDS NIH HHS R01 NS057711NINDS NIH HHS R01 NS061107NINDS NIH HHS R01 NS074387NINDS NIH HHS R01 NS076991NINDS NIH HHS R01 NS082311NINDS NIH HHS R01 NS096756NINDS NIH HHS R21 NS091555NINDS NIH HHS R37 NS094804NINDS NIH HHS T32 NS007222NINDS NIH HHS U01 NS052465
Abstract
Recent work in human glioblastoma (GBM) has documented recurrent mutations in the histone chaperone protein ATRX. We developed an animal model of ATRX-deficient GBM and showed that loss of ATRX reduces median survival and increases genetic instability. Further, analysis of genome-wide data for human gliomas showed that ATRX mutation is associated with increased mutation rate at the single-nucleotide variant (SNV) level. In mouse tumors, ATRX deficiency impairs nonhomologous end joining and increases sensitivity to DNA-damaging agents that induce double-stranded DNA breaks. We propose that ATRX loss results in a genetically unstable tumor, which is more aggressive when left untreated but is more responsive to double-stranded DNA-damaging agents, resulting in improved overall survival.
Indexed as
DNA End-Joining RepairAnimalsBrain NeoplasmsCell ProliferationChromosomes, MammalianDisease Models, AnimalDNA Copy Number VariationsDNA DamageDNA HelicasesGliomaHumansMiceMicrosatellite InstabilityMutationNuclear ProteinsPolymorphism, Single NucleotideATRX protein, humanAtrx protein, mouseDNA HelicasesNuclear ProteinsTransposasesX-linked Nuclear Protein
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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.