ArticleCell reports2022
ATRX loss in glioma results in dysregulation of cell-cycle phase transition and ATM inhibitor radio-sensitization.
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Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 71 citations in OpenAlex.
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- Whole genome and exome sequencing of pancreatic neuroendocrine tumour to investigate PRRT response.Endocrine-related cancer · 2026Article
- ATRX inactivation disrupts global chromatin state and topology to dysregulate neurodevelopmental pathways in glioma pathogenesis.Nucleic acids research · 2026Article
- Review
- Targeted therapies in pediatric oncology: A start.Molecular therapy. Oncology · 2026Review
- ATRX loss couples genome instability at a G-rich repeat to dysregulation of human alpha-globin expression.Nature communications · 2026Article
- Characterization and clinical implications of CpG island methylator phenotypes of resistant tumors.Clinical epigenetics · 2026Article
- From Classical to Emerging Biomarkers of Brain and Central Nervous System Tumors. An Evidence-Based Review with a Focus on Gliomas.Cellular and molecular neurobiology · 2026Review
- Explainable incremental-value analysis of apparent diffusion coefficient and arterial spin labeling radiomics for ATRX status prediction in glioblastoma.Frontiers in oncology · 2026Article
- Immunotherapy and targeted therapy for high grade gliomas: current and future directions.Journal of neuro-oncology · 2025Review
- Transcriptional patterns of cancer-related genes in primary and metastatic tumours revealed by machine learning.BMC biology · 2025Article
- G-quadruplex stabilizer CX-5461 effectively combines with radiotherapy to target α-thalassemia/mental retardation X-linked-deficient malignant glioma.Neuro-oncology · 2025Article
- High-grade astrocytoma with piloid features: a single-institution case series and literature review.Acta neuropathologica communications · 2025Review
- Multi-omic analysis of SDHB-deficient pheochromocytomas and paragangliomas identifies metastasis and treatment-related molecular profiles.Nature communications · 2025Article
- Precision radiotherapy with molecular-profiling of CNS tumours.Journal of neuro-oncology · 2025Review
- Advances in Glioblastoma Diagnosis: Integrating Genetics, Noninvasive Sampling, and Advanced Imaging.Cancers · 2025Review
- FACT inhibitor CBL0137, administered in an optimized schedule, potentiates radiation therapy for glioblastoma by suppressing DNA damage repair.Journal of neuro-oncology · 2024Article
- FACT inhibitor CBL0137, administered in an optimized schedule, potentiates radiation therapy for glioblastoma by suppressing DNA damage repair.Research square · 2024Article
- BTK Expression Level Prediction and the High-Grade Glioma Prognosis Using Radiomic Machine Learning Models.Journal of imaging informatics in medicine · 2024Article
- Multi-omic analysis of SDHB-deficient pheochromocytomas and paragangliomas identifies metastasis and treatment-related molecular profiles.Research square · 2024Article
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Authors and funding
27 authors at 4 institutions in 1 country.
Tingting QinDepartment of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Rogel Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Brendan MullanDepartment of Pediatrics, Division of Pediatric Hematology-Oncology, University of Michigan Medical School, 3520D MSRB 1, 1150 W Medical Center Drive, Ann Arbor, MI 48109, USA.
Ramya RavindranDepartment of Pediatrics, Division of Pediatric Hematology-Oncology, University of Michigan Medical School, 3520D MSRB 1, 1150 W Medical Center Drive, Ann Arbor, MI 48109, USA.
Dana MessingerDepartment of Pediatrics, Division of Pediatric Hematology-Oncology, University of Michigan Medical School, 3520D MSRB 1, 1150 W Medical Center Drive, Ann Arbor, MI 48109, USA.
Ruby SiadaDepartment of Pediatrics, Division of Pediatric Hematology-Oncology, University of Michigan Medical School, 3520D MSRB 1, 1150 W Medical Center Drive, Ann Arbor, MI 48109, USA.
Jessica R CummingsDepartment of Pediatrics, Division of Pediatric Hematology-Oncology, University of Michigan Medical School, 3520D MSRB 1, 1150 W Medical Center Drive, Ann Arbor, MI 48109, USA.
Micah HarrisDepartment of Pediatrics, Division of Pediatric Hematology-Oncology, University of Michigan Medical School, 3520D MSRB 1, 1150 W Medical Center Drive, Ann Arbor, MI 48109, USA.
Ashwath MuruganandDepartment of Pediatrics, Division of Pediatric Hematology-Oncology, University of Michigan Medical School, 3520D MSRB 1, 1150 W Medical Center Drive, Ann Arbor, MI 48109, USA.
Kalyani PyaramDivision of Biology, Kansas State University, Manhattan, KS 66506, USA.
Zachary MikljaDepartment of Pediatrics, Division of Pediatric Hematology-Oncology, University of Michigan Medical School, 3520D MSRB 1, 1150 W Medical Center Drive, Ann Arbor, MI 48109, USA.
Mary ReiberDepartment of Pediatrics, Division of Pediatric Hematology-Oncology, University of Michigan Medical School, 3520D MSRB 1, 1150 W Medical Center Drive, Ann Arbor, MI 48109, USA.
Taylor GarciaDepartment of Pediatrics, Division of Pediatric Hematology-Oncology, University of Michigan Medical School, 3520D MSRB 1, 1150 W Medical Center Drive, Ann Arbor, MI 48109, USA.
Dustin TranDepartment of Pediatrics, Division of Pediatric Hematology-Oncology, University of Michigan Medical School, 3520D MSRB 1, 1150 W Medical Center Drive, Ann Arbor, MI 48109, USA.
Carla DanussiDepartment of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Jacqueline Brosnan-CashmanDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Drew PrattDepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Xinyi ZhaoDepartment of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Alnawaz RehemtullaDepartment of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Maureen A SartorDepartment of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Sriram VennetiDepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Alan K MeekerDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Jason T HuseDepartment of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Meredith A MorganDepartment of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Pedro R LowensteinDepartments of Neurosurgery and Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Maria G CastroDepartments of Neurosurgery and Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Viveka Nand YadavDepartment of Pediatrics, Division of Pediatric Hematology-Oncology, University of Michigan Medical School, 3520D MSRB 1, 1150 W Medical Center Drive, Ann Arbor, MI 48109, USA.
Carl KoschmannDepartment of Pediatrics, Division of Pediatric Hematology-Oncology, University of Michigan Medical School, 3520D MSRB 1, 1150 W Medical Center Drive, Ann Arbor, MI 48109, USA. Electronic address: ckoschma@med.umich.edu.
University of Michigan · USJohns Hopkins University · USThe University of Texas MD Anderson Cancer Center · USKansas State University · US
Funding
XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI THEODORE S LAWRENCE · 1988 to 2026
$178.2MStrategic Vision & Impact on Environmental HealthP30ES017885 · NIEHS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Dana Dolinoy · 2011 to 2026
$21.3MTraining Program in Tumor MicroenvironmentT32CA009676 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Maria G Castro, Analisa Virginia DiFeo · 1992 to 2026
$7.3MSensitization to Chemoradiation by Therapeutic Targeting of the DNA Damage ResponseU01CA216449 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LAWRENCE, THEODORE S · 2017 to 2021
$3.0MImmune-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
$2.9MUnravelling metabolic dependencies in H3K27M mutant DIPGR01NS110572 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Sriram Venneti · 2019 to 2026
$2.7MUncover the role of H3.3-G343R mutation in shaping the DNA damage response, anti-tumor immunity and mechanisms of resistance in glioma.R01NS122165 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Maria G Castro · 2022 to 2026
$2.5MThe Role of Collagen and its Signaling Mechanisms in Glioma Progression and Invasion.R01NS122234 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Pedro R. Lowenstein · 2022 to 2026
$2.4MTargeting the DNA damage response in combination with radiation to induce innate immunity and improve immunotherapy efficacy in pancreatic cancerR01CA240515 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MORGAN, MEREDITH A · 2020 to 2024
$2.2MNeuroimmunology of Malignant Brain Tumors: Innate MechanismsR01NS096756 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LOWENSTEIN, PEDRO R. · 2016 to 2020
$2.1MThe role of ATRX mutation in the epigenetic dysregulation of cell cycle in pediatric high-grade gliomaR01NS119231 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KOSCHMANN, CARL J · 2021 to 2025
$1.9MInteractions between the tumor cells and the neuro-immune microenvironment in mutant IDH1 gliomas: implications for therapeuticsR01NS105556 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CASTRO, MARIA G · 2018 to 2021
$1.9MNCI NIH HHS P30 CA046592NCI NIH HHS R01 CA240515NCI NIH HHS T32 CA009676NCI NIH HHS U01 CA216449NIEHS NIH HHS P30 ES017885NINDS NIH HHS K08 NS099427NINDS NIH HHS R01 NS082311NINDS NIH HHS R01 NS096756NINDS NIH HHS R01 NS105556NINDS NIH HHS R01 NS110572NINDS NIH HHS R01 NS119231NINDS NIH HHS R01 NS122165NINDS NIH HHS R01 NS122234NINDS NIH HHS R21 NS107894NINDS NIH HHS R37 NS094804
Abstract
ATRX, a chromatin remodeler protein, is recurrently mutated in H3F3A-mutant pediatric glioblastoma (GBM) and isocitrate dehydrogenase (IDH)-mutant grade 2/3 adult glioma. Previous work has shown that ATRX-deficient GBM cells show enhanced sensitivity to irradiation, but the etiology remains unclear. We find that ATRX binds the regulatory elements of cell-cycle phase transition genes in GBM cells, and there is a marked reduction in Checkpoint Kinase 1 (CHEK1) expression with ATRX loss, leading to the early release of G2/M entry after irradiation. ATRX-deficient cells exhibit enhanced activation of master cell-cycle regulator ATM with irradiation. Addition of the ATM inhibitor AZD0156 doubles median survival in mice intracranially implanted with ATRX-deficient GBM cells, which is not seen in ATRX-wild-type controls. This study demonstrates that ATRX-deficient high-grade gliomas (HGGs) display Chk1-mediated dysregulation of cell-cycle phase transitions, which opens a window for therapies targeting this phenotype.
Indexed as
AnimalsBrain NeoplasmsCell CycleCell Cycle CheckpointsCell Line, TumorCheckpoint Kinase 1FemaleGliomaHistonesHumansIsocitrate DehydrogenaseMaleMiceMice, Inbred C57BLMutationNeoplasm Recurrence, LocalATRX protein, humanAtrx protein, mouseCheckpoint Kinase 1CHEK1 protein, humanChek1 protein, mouseHistonesIsocitrate DehydrogenaseX-linked Nuclear ProteinATM inhibitorATRXcell-cycleCHEK1epigeneticsglioma
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