ArticleNature cancer2022
Loss of MAT2A compromises methionine metabolism and represents a vulnerability in H3K27M mutant glioma by modulating the epigenome.
Erratum issuedOpen access · greenAbstract read
In one paragraph
Article in Nature cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 34 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 1 pooled it
13.3field-weighted citation impact, top 1% of its field
What it found
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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.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 89 citations in OpenAlex.
- Metabolic modulation of glioblastoma by dietary intervention: a systematic review.Journal of neuro-oncology · 2026Pooled it
- Integrating proteomics and metabolomics to reveal MAT2A for metabolic reprogramming in non-small cell lung cancer cells.iScience · 2026Article
- Article
- Role of methionine metabolism in cancer: recent advances in molecular mechanisms and therapeutic implications.Experimental hematology & oncology · 2026Review
- Emerging roles of ferroptosis in modulating the immune landscape of glial tumours.Nature cell biology · 2026Review
- Hp1bp3 loss links chromatin reorganization to metabolic vulnerability in glioma.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Dynamic remodeling of amino acid metabolism in tumor-associated macrophages: Fueling immunosuppression, reshaping tumor niches, and unlocking metabolic checkpoints.Journal of advanced research · 2026Review
- Methionine restriction and mimetics to ameliorate human aging and disease.Trends in endocrinology and metabolism: TEM · 2026Review
- Targeting the Mapk13-Tcf1-Slc7a5 Axis via One-Carbon Metabolic Regulation to Prevent Chronic Allograft Vasculopathy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- H3K27M diffuse midline glioma is homologous recombination defective and sensitized to radiotherapy and NK cell-mediated antitumor immunity by PARP inhibition.Neuro-oncology · 2025Article
- The Landscape of Cancer Metabolism as a Therapeutic Target.Pathology international · 2025Review
- Glioma promotes macrophage immunosuppressive phenotype through ANXA1 in a methionine metabolism-dependent manner.Discover oncology · 2025Article
- Current Landscape of Preclinical Models for Pediatric Gliomas: Clinical Implications and Future Directions.Cancers · 2025Review
- Amino acids in cancer: Understanding metabolic plasticity and divergence for better therapeutic approaches.Cell reports · 2025Review
- Metabolism-driven chromatin dynamics: Molecular principles and technological advances.Molecular cell · 2025Review
- Methionine restriction promotes the polarization of macrophages towards M1 and the immunotherapy effect of PD-L1/PD-1 blockades by inhibiting the secretion of MIF by gastric carcinoma cells.Translational oncology · 2025Article
- Emerging roles for methionine metabolism in immune cell fate and function.Frontiers in immunology · 2025Review
- Deep mutual learning on hybrid amino acid PET predicts H3K27M mutations in midline gliomas.NPJ precision oncology · 2024Article
- MAT2a and AHCY inhibition disrupts antioxidant metabolism and reduces glioblastoma cell survival.bioRxiv : the preprint server for biology · 2024Article
- Therapeutic targeting of differentiation-state dependent metabolic vulnerabilities in diffuse midline glioma.Nature communications · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
49 authors at 13 institutions in 4 countries.
Brian J GolbournDepartment of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Matthew E HalbertDepartment of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Katharine HalliganDepartment of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Srinidhi VaradharajanBaylor College of Medicine, Texas Children's Cancer and Hematology Centers, Dan L. Duncan Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-2033-0758
Brian KrugDepartment of Human Genetics, McGill University, Montreal, Quebec, Canada.
Nneka E MbahDepartment of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA.
Nisha KabirDepartment of Human Genetics, McGill University, Montreal, Quebec, Canada.
Ann-Catherine J StantonDepartment of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Abigail L LockeDepartment of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Stephanie M CasilloDepartment of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Yanhua ZhaoBaylor College of Medicine, Texas Children's Cancer and Hematology Centers, Dan L. Duncan Cancer Center, Houston, TX, USA.
Lauren M SandersDepartment of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, CA, USA.
Allison CheneyDepartment of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, CA, USA.ORCID http://orcid.org/0000-0003-1435-6190
Steven J MullettDepartment of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA.
Apeng ChenDepartment of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0002-1936-2007
Michelle WassellDepartment of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Anthony AndrenDepartment of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA.
Jennifer PerezDepartment of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Esther P JaneDepartment of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Daniel R David PremkumarDepartment of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Robert F KoncarDepartment of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0001-6180-3198
Shideh MirhadiDepartment of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Lauren H McCarlDepartment of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Yue-Fang ChangDepartment of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Yijen L WuDepartment of Developmental Biology, University of Pittsburgh and Rangos Research Center Animal Imaging Core, Pittsburgh, PA, USA.
Taylor A GatesmanDepartment of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Andrea F CruzDepartment of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Michal ZapotockyDepartment of Pediatric Hematology and Oncology, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.ORCID http://orcid.org/0000-0002-9013-2546
Baoli HuDepartment of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Gary KohanbashDepartment of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Xiuxing WangDepartment of Cell Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China.ORCID http://orcid.org/0000-0002-5993-9368
Alenoush VartanianDepartment of Pharmacy, UPMC Shadyside, Pittsburgh, PA, USA.
Michael F MoranDepartment of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Frank LiebermanDepartment of Neurology, Adult Neurooncology Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Nduka M AmankulorDepartment of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Stacy G WendellDepartment of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA.
Olena M VaskeDepartment of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, CA, USA.
Ashok PanigrahyDepartment of Radiology, Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
James FelkerPediatric Neuro-Oncology Program, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
Kelsey C BertrandDepartment of Pediatric Hematology and Oncology, St Jude Children's Research Hospital, Memphis, TN, USA.
Claudia L KleinmanDepartment of Human Genetics, McGill University, Montreal, Quebec, Canada.ORCID http://orcid.org/0000-0002-5158-7126
Jeremy N RichDepartment of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Robert M FriedlanderDepartment of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Alberto BroniscerJohn G. Rangos Sr. Research Center, Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
Costas LyssiotisDepartment of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0001-9309-6141
Nada JabadoDepartment of Human Genetics, McGill University, Montreal, Quebec, Canada.ORCID http://orcid.org/0000-0003-2485-3692
Ian F PollackDepartment of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Stephen C MackBaylor College of Medicine, Texas Children's Cancer and Hematology Centers, Dan L. Duncan Cancer Center, Houston, TX, USA. stephen.mack@stjude.org.ORCID http://orcid.org/0000-0001-9620-4742
Sameer AgnihotriDepartment of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. sameer.agnihotri@pitt.edu.ORCID http://orcid.org/0000-0001-6584-3795
University of Pittsburgh · USChildren's Hospital of Pittsburgh · USUniversity of California, Santa Cruz · USUniversity of Michigan · USBaylor College of Medicine · USJewish General Hospital · CAMcGill University Health Centre · CASt. Jude Children's Research Hospital · USUniversity of Toronto · CACharles University · CZNanjing Medical University · CNShadyside Hospital · USUPMC Hillman Cancer Center · US
Funding
VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Jessie Nedrow · 1988 to 2026
$158.0MTraining Program in Molecular, Cell, and Developmental BiologyT32GM133391 · NIGMS · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI Needhi Bhalla · 2019 to 2026
$3.0MDeciphering the Role of Aberrant Endogenous Retroviral Expression in Onco-histone Driven GliomaR01NS116361 · NINDS · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI Stephen C Mack · 2021 to 2026
$2.5MTargeting extracellular signaling-regulated kinase 5 (ERK5) in brain tumors and their microenvironmentR01NS115831 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI AGNIHOTRI, SAMEER · 2020 to 2024
$1.8MBringing Untargeted Metabolomics to PittS10OD023402 · OD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GELHAUS, STACY LYNN · 2018 to 2018
$594kNCI NIH HHS P30 CA047904NIGMS NIH HHS T32 GM133391NIH HHS S10 OD023402NINDS NIH HHS R01 NS115831NINDS NIH HHS R01 NS116361
Abstract
Diffuse midline gliomas (DMGs) bearing driver mutations of histone 3 lysine 27 (H3K27M) are incurable brain tumors with unique epigenomes. Here, we generated a syngeneic H3K27M mouse model to study the amino acid metabolic dependencies of these tumors. H3K27M mutant cells were highly dependent on methionine. Interrogating the methionine cycle dependency through a short-interfering RNA screen identified the enzyme methionine adenosyltransferase 2A (MAT2A) as a critical vulnerability in these tumors. This vulnerability was not mediated through the canonical mechanism of MTAP deletion; instead, DMG cells have lower levels of MAT2A protein, which is mediated by negative feedback induced by the metabolite decarboxylated S-adenosyl methionine. Depletion of residual MAT2A induces global depletion of H3K36me3, a chromatin mark of transcriptional elongation perturbing oncogenic and developmental transcriptional programs. Moreover, methionine-restricted diets extended survival in multiple models of DMG in vivo. Collectively, our results suggest that MAT2A presents an exploitable therapeutic vulnerability in H3K27M gliomas.
Indexed as
Brain NeoplasmsGliomaAnimalsEpigenomeHistonesMethionineMethionine AdenosyltransferaseMiceHistonesMat2a protein, mouseMethionineMethionine Adenosyltransferase
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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.