ArticleCell2022
Glioma progression is shaped by genetic evolution and microenvironment interactions.
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Article in Cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 308 papers.
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308citing papers in PubMed
80.2field-weighted citation impact, top 1% of its field
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Who cites it
308 citing papers in PubMed, 468 citations in OpenAlex.
- Improved overall survival in an anti-PD-L1 treated cohort of newly diagnosed glioblastoma patients is associated with distinct immune, mutation, and gut microbiome features: a single arm prospective phase I/II trial.Nature communications · 2025Trial
- High levels of nitric oxide and peroxynitrite with protein nitration: a new therapeutic target for gliomas.Medical gas research · 2027Review
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- The Imbalance Between Tumor Immunosurveillance and Tumor Immune Escape in Glioblastoma.Immunology and cell biology · 2026Review
- A State-Resolved Single-Cell and Spatial Atlas RevealsMedComm · 2026Article
- Precision virotherapy for IDH-mutant astrocytoma.Molecular therapy. Oncology · 2026Article
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- Gliomas phenocopy an inborn error of metabolism to drive neuronal activity and tumor growth.Cell · 2026Article
- Multi-sampling allows intra-tumoral heterogeneity querying and vulnerability profiling in glioblastoma.Neuro-oncology · 2026Article
- Persistent chromatin alterations and gene expression reprogramming follow widespread DNA damage in glioblastoma.Nature communications · 2026Article
- Systemic and local dysregulation of the complement system in glioma: a comprehensive systematic review.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- The Invasive Margin of Glioblastoma as a Molecular Ecosystem: Spatial Heterogeneity, Tumor-Host Interactions, and Therapeutic Opportunities.International journal of molecular sciences · 2026Review
- Exploring the landscape of targetable alterations in patients with glioblastoma.Nature reviews. Clinical oncology · 2026Review
- IDH-Mutant Diffuse Glioma: From Metabolic Origins to Targeted Therapy.Journal of clinical medicine · 2026Review
- EDNRB-dependent endothelin signaling reduces proliferation and promotes proneural-to-mesenchymal transition in gliomas.Molecular oncology · 2026Article
- Mechanisms, Microenvironments, and Models: Understanding Therapeutic Resistance in Glioblastoma.International journal of radiation oncology, biology, physics · 2026Review
- Spatial Omics Technologies in Glioblastoma Research: Principles, Applications, and Best Practices.Genes · 2026Review
- Circulating immune profiling reveals impaired monocyte states and trajectories driving immunosuppression in glioblastoma.Journal of neuroinflammation · 2026Article
- IL6 Supports Development of an Immunosuppressive Microenvironment and Resistance to Therapy in Glioblastoma.Cancer research · 2026Article
- Article
248 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
50 authors at 20 institutions in 11 countries.
Frederick S VarnThe Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
Kevin C JohnsonThe Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
Jan MartinekThe Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
Jason T HuseDepartment of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
MacLean P NasrallahDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Pieter WesselingAmsterdam University Medical Centers/VUmc, Amsterdam, the Netherlands; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Lee A D CooperDepartment of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Tathiane M MaltaSchool of Pharmaceutical Sciences of Ribeirao Preto, University of São Paulo, Brazil, Ribeirao Preto, São Paulo, Brazil.
Taylor E WadeThe Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
Thais S SabedotHermelin Brain Tumor Center, Henry Ford Health System, Detroit, MI, USA.
Daniel BratDepartment of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Peter V Gouldservice d'anatomopathologie, Hôpital de l'Enfant-Jésus du Centre hospitalier universitaire de Québec, Université Laval, Quebec City, QC, Canada.
Adelheid WöehrerDivision of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria.
Kenneth AldapeNational Cancer Institute, Bethesda, MD, USA.
Azzam IsmailDepartment of Cellular and Molecular Pathology, Leeds Teaching Hospital NHS Trust, St James's University Hospital, Leeds, UK.
Santhosh K SivajothiThe Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
Floris P BarthelThe Jackson Laboratory for Genomic Medicine, Farmington, CT, USA; Cancer and Cell Biology Division, the Translational Genomics Research Institute, Phoenix, AZ, USA.
Hoon KimThe Jackson Laboratory for Genomic Medicine, Farmington, CT, USA; Department of Biopharmaceutical Convergence, Department of Pharmacy, Sungkyunkwan University, Suwon-si, Gyeong gi-do, South Korea.
Emre KocakavukThe Jackson Laboratory for Genomic Medicine, Farmington, CT, USA; Department of Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, Essen, Germany.
Nazia AhmedUniversity of Leeds, Leeds, UK.
Kieron WhitePrecision Cancer Medicine Group, Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, D02 YN77 Dublin, Ireland.
Indrani DattaDepartment of Public Health Sciences, Hermelin Brain Tumor Center, Henry Ford Health System, Detroit, MI, USA.
Hyo-Eun MoonSeoul National University College of Medicine and Seoul National University Hospital, Seoul, Republic of Korea.
Steven PollockUniversity of Leeds, Leeds, UK.
Christine GoldfarbThe Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
Ga-Hyun LeeThe Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
Luciano GarofanoInstitute for Cancer Genetics, Columbia University Medical Center, New York, NY, USA.
Kevin J AndersonThe Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
Djamel Nehar-BelaidThe Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
Jill S Barnholtz-SloanCase Western Reserve University School of Medicine and University Hospitals of Cleveland, Cleveland, OH, USA; Center for Biomedical Informatics and Information Technology & Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Spyridon BakasDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA.
Annette T ByrnePrecision Cancer Medicine Group, Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, D02 YN77 Dublin, Ireland.
Fulvio D'AngeloInstitute for Cancer Genetics, Columbia University Medical Center, New York, NY, USA.
Hui K GanOlivia Newton-John Cancer Research Institute, Austin Health, Melbourne, Australia.
Mustafa KhasrawPreston Robert Tisch Brain Tumor Center at Duke, Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA.
Simona MigliozziInstitute for Cancer Genetics, Columbia University Medical Center, New York, NY, USA.
D Ryan OrmondDepartment of Neurosurgery, University of Colorado School of Medicine, Aurora, CO, USA.
Sun Ha PaekSeoul National University College of Medicine and Seoul National University Hospital, Seoul, Republic of Korea.
Erwin G Van MeirDepartment of Neurosurgery, School of Medicine and O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA.
Annemiek M E WalenkampDepartment of Medical Oncology, University Medical Center Groningen, Groningen, the Netherlands.
Colin WattsAcademic Department of Neurosurgery, Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.
Tobias WeissDepartment of Neurology, Clinical Neuroscience Center, University Hospital Zurich and University of Zürich, Switzerland.
Michael WellerDepartment of Neurology, Clinical Neuroscience Center, University Hospital Zurich and University of Zürich, Switzerland.
Karolina PaluckaThe Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
Lucy F SteadUniversity of Leeds, Leeds, UK.
Laila M PoissonDepartment of Public Health Sciences, Hermelin Brain Tumor Center, Henry Ford Health System, Detroit, MI, USA.
Houtan NoushmehrHermelin Brain Tumor Center, Henry Ford Health System, Detroit, MI, USA.
Antonio IavaroneInstitute for Cancer Genetics, Columbia University Medical Center, New York, NY, USA; Department of Neurology, Columbia University Medical Center, New York, NY, USA; Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USA.
Roel G W VerhaakThe Jackson Laboratory for Genomic Medicine, Farmington, CT, USA; Department of Neurosurgery, Amsterdam University Medical Centers/VUmc, Amsterdam, the Netherlands. Electronic address: roel.verhaak@jax.org.
GLASS Consortium
Jackson Laboratory · USColumbia University Irving Medical Center · USHenry Ford Health System · USUniversity of Leeds · GBUniversity of Zurich · CHRoyal College of Surgeons in Ireland · IEUniversity of Pennsylvania · USNorthwestern University · USSeoul National University Hospital · KRUniversity Hospitals of Cleveland · USHôpital de l'Enfant-Jésus · CATranslational Genomics Research Institute · USUniversity Medical Center Groningen · NLDuke Medical Center · USMedical University of Vienna · ATNational Cancer Institute · USOlivia Newton-John Cancer Wellness & Research Centre · AUPrincess Máxima Center · NLSt James's University Hospital · GBThe University of Texas MD Anderson Cancer Center · US
Funding
Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8MXRAY CRYSTALLOGRAPHYP30CA013148 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Robert S Welner · 1985 to 2026
$165.9MShared Resource ManagementP30CA034196 · NCI · JACKSON LABORATORY · PI William Carl Skarnes · 1985 to 2026
$61.9MTissue CoreP50CA097257 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Joseph F Costello · 2002 to 2026
$57.4MTropism Enhanced Oncolytic Adenovirus for the Treatment of Brain TumorsP50CA127001 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Juan Fueyo · 2008 to 2026
$41.2MParticipant Engagement UnitU2CCA252979 · NCI · YALE UNIVERSITY · PI elizabeth B. claus · 2021 to 2026
$15.5MStatistical atlases of brain tumor MRI:do imaging phenotypes predict progression?R01NS042645 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI DAVATZIKOS, CHRISTOS · 2002 to 2024
$8.7MGenetic evolution of glioblastomas during radiation and temozolomide therapyR01CA188228 · NCI · DANA-FARBER CANCER INST · PI BEROUKHIM, RAMEEN, CHAKRAVARTI, ARNAB · 2015 to 2025
$6.9MGenomic Biomarkers of CancerZIABC011850 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI ALDAPE, KENNETH · 2019 to 2025
$5.1MCancer imaging phenomics software suite: application to brain and breast cancerU24CA189523 · NCI · UNIVERSITY OF PENNSYLVANIA · PI DAVATZIKOS, CHRISTOS, KONTOS, DESPINA · 2015 to 2019
$3.2MMolecular and clinical evaluation of the glioma patient experience to anticipate modern outcomes and guide patient careR01CA222146 · NCI · HENRY FORD HEALTH SYSTEM · PI POISSON, LAILA M · 2018 to 2023
$2.8M3-D spatial approach to discover genomic effectors of immunosuppression during malignant transformationR01CA244838 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI COSTELLO, JOSEPH F · 2020 to 2024
$2.7MMedical Research Council MR/T020504/1NCI NIH HHS K99 CA226387NCI NIH HHS P30 CA013148NCI NIH HHS P30 CA016672NCI NIH HHS P30 CA034196NCI NIH HHS P50 CA097257NCI NIH HHS P50 CA127001NCI NIH HHS R01 CA188228NCI NIH HHS R01 CA218144NCI NIH HHS R01 CA222146NCI NIH HHS R01 CA237208NCI NIH HHS R01 CA244838NCI NIH HHS R21 CA256575NCI NIH HHS R33 CA236681NCI NIH HHS U01 CA242871NCI NIH HHS U24 CA189523NCI NIH HHS U2C CA252979NINDS NIH HHS R01 NS042645NINDS NIH HHS R01 NS094615NINDS NIH HHS R21 NS114873
Abstract
The factors driving therapy resistance in diffuse glioma remain poorly understood. To identify treatment-associated cellular and genetic changes, we analyzed RNA and/or DNA sequencing data from the temporally separated tumor pairs of 304 adult patients with isocitrate dehydrogenase (IDH)-wild-type and IDH-mutant glioma. Tumors recurred in distinct manners that were dependent on IDH mutation status and attributable to changes in histological feature composition, somatic alterations, and microenvironment interactions. Hypermutation and acquired CDKN2A deletions were associated with an increase in proliferating neoplastic cells at recurrence in both glioma subtypes, reflecting active tumor growth. IDH-wild-type tumors were more invasive at recurrence, and their neoplastic cells exhibited increased expression of neuronal signaling programs that reflected a possible role for neuronal interactions in promoting glioma progression. Mesenchymal transition was associated with the presence of a myeloid cell state defined by specific ligand-receptor interactions with neoplastic cells. Collectively, these recurrence-associated phenotypes represent potential targets to alter disease progression.
Indexed as
Brain NeoplasmsGliomaTumor MicroenvironmentAdultEvolution, MolecularGenes, p16HumansIsocitrate DehydrogenaseMutationNeoplasm Recurrence, LocalIsocitrate Dehydrogenasegenomicsglioblastomagliomahypermutationmacrophagesmicroenvironmentneuronssingle-cellspatial imagingtreatment resistance
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