ArticleCancer discovery2022
BAF Complex Maintains Glioma Stem Cells in Pediatric H3K27M Glioma.
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Article in Cancer discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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47citing papers in PubMed
4.8field-weighted citation impact, top 4% of its field
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47 citing papers in PubMed, 61 citations in OpenAlex.
- Selective histone deacetylase inhibition as a therapeutically relevant strategy in H3K27M-glioma.Neuro-oncology · 2026Article
- The roles of chromatin remodeling and 3D genome organization in cancers: from mechanistic insights to emerging treatment options.Molecular cancer · 2026Review
- BAF chromatin remodeling complexes inhibit immediate-early and early, but not late, transcription of herpes simplex virus 1.bioRxiv : the preprint server for biology · 2026Article
- Combinatorial Targeting of Avapritinib-Driven MAP Kinase Activation in High-Grade Glioma.Research square · 2026Article
- Canonical BAF chromatin remodeling complex specifies stem cell fate via cell-type-specific co-factor recruitment.Nature communications · 2026Article
- Chromatin Accessibility in Cancer: Biological Functions, Mechanisms, Therapeutic Potential, and Future Directions.MedComm · 2026Review
- SAGA/ATAC complexes sustain aberrant chromatin regulation and promote tumorigenesis in diffuse midline glioma.bioRxiv : the preprint server for biology · 2026Article
- Novel modifiers of oncoprotein-mediated Polycomb inhibition in Drosophila melanogaster.Genetics · 2025Article
- Systematic decoding of functional enhancer connectomes and risk variants in human glioma.Nature cell biology · 2025Article
- Role of nuclear ATPases in nuclear mechanics and cell migration through confined spaces: opposite effects of BRG1 and cohesin.bioRxiv : the preprint server for biology · 2025Article
- Role of lysine acetylation-related genes in the diagnosis and prognosis of glioma.Scientific reports · 2025Article
- Cancer Stem Cells Connecting to Immunotherapy: Key Insights, Challenges, and Potential Treatment Opportunities.Cancers · 2025Review
- A specific form of cPRC1 containing CBX4 is co-opted to mediate oncogenic gene repression in diffuse midline glioma.Molecular cell · 2025Article
- Investigating oncoprotein-mediated chromatin dysregulation inbioRxiv : the preprint server for biology · 2025Article
- Death-ision: the link between cellular resilience and cancer resistance to treatments.Molecular cancer · 2025Review
- Chromatin remodeling and cancer: the critical influence of the SWI/SNF complex.Epigenetics & chromatin · 2025Review
- An oncohistone-driven H3.3K27M/CREB5/ID1 axis maintains the stemness and malignancy of diffuse intrinsic pontine glioma.Nature communications · 2025Article
- Article
- Cancer stem cells and niches: challenges in immunotherapy resistance.Molecular cancer · 2025Review
- Epigenetic modifications and their roles in pediatric brain tumor formation: emerging insights from chromatin dysregulation.Frontiers in oncology · 2025Review
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Authors and funding
55 authors at 11 institutions in 4 countries.
Eshini Panditharatna *Department of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts.ORCID 0000-0002-4530-7298
Joana G Marques *Department of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts.ORCID 0000-0001-7152-9655
Tingjian WangDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0003-2203-9590
Maria C TrissalDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts.ORCID 0000-0003-2861-658X
Ilon LiuDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts.ORCID 0000-0002-6186-3630
Li JiangDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts.ORCID 0000-0001-7320-5283
Alexander BeckCenter for Neuropathology, Ludwig Maximilian University of Munich, Munich, Germany.ORCID 0000-0001-8641-7832
Andrew GrovesDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts.ORCID 0000-0002-1239-3839
Neekesh V DhariaDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts.ORCID 0000-0001-5048-067X
Deyao LiDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0003-2980-3483
Samantha E HoffmanDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts.ORCID 0000-0002-6752-172X
Guillaume KugenerBroad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts.ORCID 0000-0002-4697-2847
McKenzie L ShawDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts.ORCID 0000-0003-3734-5312
Hafsa M MireDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts.ORCID 0000-0001-9293-2953
Olivia A HackDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts.ORCID 0000-0003-3962-1560
Joshua M DempsterBroad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts.ORCID 0000-0002-3634-9576
Caleb LareauBroad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts.ORCID 0000-0003-4179-4807
Lingling DaiDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0001-5345-5824
Logan H SiguaDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0002-1469-5398
Michael A QuezadaDepartment of Neurology, Stanford University School of Medicine, Stanford, California.ORCID 0000-0001-7307-5204
Ann-Catherine J StantonDepartment of Neurosurgery, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.ORCID 0000-0003-2310-3670
Meghan WyattBroad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts.ORCID 0000-0003-3236-9921
Zohra KalaniBroad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts.ORCID 0000-0003-2707-8097
Amy GoodaleBroad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts.ORCID 0000-0003-4294-5777
Francisca VazquezBroad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts.ORCID 0000-0002-2857-4685
Federica PiccioniBroad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts.ORCID 0000-0003-1210-3210
John G DoenchBroad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts.ORCID 0000-0002-3707-9889
David E RootBroad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts.ORCID 0000-0001-5122-861X
Jamie N AnastasDivision of Newborn Medicine and Epigenetics Program, Department of Medicine, Boston Children's Hospital, Boston, Massachusetts.ORCID 0000-0002-5317-5352
Kristen L JonesLurie Family Imaging Center, Center for Biomedical Imaging in Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0002-8688-6679
Amy Saur ConwayDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts.ORCID 0000-0002-7416-6076
Sylwia StopkaDepartment of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.ORCID 0000-0003-3761-6899
Michael S ReganDepartment of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.ORCID 0000-0001-5252-2829
Yu LiangDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0001-7832-5110
Hyuk-Soo SeoDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0003-0646-2102
Kijun SongDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0002-6037-9345
Puspalata BashyalDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0002-7145-7660
William P JeromeDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts.ORCID 0000-0002-0683-9603
Nathan D MathewsonDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-8895-2609
Sirano Dhe-PaganonDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0003-0824-5929
Mario L SuvàDepartment of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0001-9898-5351
Angel M CarcabosoDevelopmental Tumor Biology Laboratory, Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain.ORCID 0000-0002-8485-426X
Cinzia LavarinoDevelopmental Tumor Biology Laboratory, Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain.ORCID 0000-0002-9630-3676
Jaume MoraDevelopmental Tumor Biology Laboratory, Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain.ORCID 0000-0002-9386-5980
Quang-De NguyenLurie Family Imaging Center, Center for Biomedical Imaging in Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Keith L LigonDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts.ORCID 0000-0002-7733-600X
Yang ShiDivision of Newborn Medicine and Epigenetics Program, Department of Medicine, Boston Children's Hospital, Boston, Massachusetts.ORCID 0000-0001-9713-1709
Sameer AgnihotriDepartment of Neurosurgery, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.ORCID 0000-0001-6584-3795
Nathalie Y R AgarDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0003-3149-3146
Kimberly StegmaierDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts.ORCID 0000-0003-0218-7895
Charles D StilesDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0003-1677-1195
Michelle MonjeDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California.ORCID 0000-0002-3547-237X
Todd R GolubDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts.ORCID 0000-0003-0113-2403
Jun QiDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0002-1461-3356
Mariella G FilbinDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts.ORCID 0000-0002-2613-8126
Broad Institute · USHarvard University · USDana-Farber/Boston Children's Cancer and Blood Disorders Center · USBrigham and Women's Hospital · USDana-Farber Cancer Institute · USHospital Sant Joan de Déu Barcelona · ESBoston Children's Hospital · USChildren's Hospital of Pittsburgh · USLudwig-Maximilians-Universität München · DEStanford Medicine · USStanford University · US
Funding
Medical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0MTargeting the Vasular SystemP50CA165962 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI WENDY Beth LONDON · 2013 to 2026
$33.5MImage Guided Therapy Center - Ultrasound-based sensor system for the monitoring of COVID-19 patientsP41EB015898 · NIBIB · BRIGHAM AND WOMEN'S HOSPITAL · PI TEMPANY, CLARE M · 2012 to 2021
$18.9MMedical Scientist Training ProgramT32GM144273 · NIGMS · HARVARD MEDICAL SCHOOL · PI David Shumway Jones, Jacqueline A. Lees · 2022 to 2026
$14.7MTRD 3 - Enabling Technologies for Intraprocedural GuidanceP41EB028741 · NIBIB · BRIGHAM AND WOMEN'S HOSPITAL · PI Carl-Fredrik Westin · 2021 to 2026
$10.7MTrans Network ProjectU54CA210180 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI WHITE, FOREST M · 2016 to 2020
$10.2MResearch Training in Pediatric OncologyT32CA136432 · NCI · DANA-FARBER CANCER INST · PI SCOTT A ARMSTRONG · 2009 to 2026
$7.9MIntegrating Transforming Approaches to Identify and Target New Vulnerabilities in CancerR35CA210030 · NCI · DANA-FARBER CANCER INST · PI STEGMAIER, KIMBERLY · 2016 to 2022
$7.3MEpigenetic regulation of cellular plasticity and cancer cell fateR35CA210104 · NCI · BOSTON CHILDREN'S HOSPITAL · PI SHI, YANG · 2017 to 2019
$2.8MHow the 3D Architecture of the Brain Shapes Cancer Cell Fate DecisionsDP2NS127705 · NINDS · DANA-FARBER CANCER INST · PI FILBIN, MARIELLA GRUBER · 2021 to 2024
$2.7MTraining in Image Guidance, Precision Diagnosis and TherapyT32EB025823 · NIBIB · BRIGHAM AND WOMEN'S HOSPITAL · PI Fiona Fennessy, Lauren Jean O'Donnell · 2019 to 2026
$1.5MNCI NIH HHS P50 CA165962NCI NIH HHS R35 CA210030NCI NIH HHS R35 CA210104NCI NIH HHS T32 CA136432NCI NIH HHS U54 CA210180NIBIB NIH HHS P41 EB015898NIBIB NIH HHS P41 EB028741NIBIB NIH HHS T32 EB025823NIGMS NIH HHS T32 GM007753NIGMS NIH HHS T32 GM144273NINDS NIH HHS DP2 NS127705
Abstract
Diffuse midline gliomas are uniformly fatal pediatric central nervous system cancers that are refractory to standard-of-care therapeutic modalities. The primary genetic drivers are a set of recurrent amino acid substitutions in genes encoding histone H3 (H3K27M), which are currently undruggable. These H3K27M oncohistones perturb normal chromatin architecture, resulting in an aberrant epigenetic landscape. To interrogate for epigenetic dependencies, we performed a CRISPR screen and show that patient-derived H3K27M-glioma neurospheres are dependent on core components of the mammalian BAF (SWI/SNF) chromatin remodeling complex. The BAF complex maintains glioma stem cells in a cycling, oligodendrocyte precursor cell-like state, in which genetic perturbation of the BAF catalytic subunit SMARCA4 (BRG1), as well as pharmacologic suppression, opposes proliferation, promotes progression of differentiation along the astrocytic lineage, and improves overall survival of patient-derived xenograft models. In summary, we demonstrate that therapeutic inhibition of the BAF complex has translational potential for children with H3K27M gliomas. SIGNIFICANCE: Epigenetic dysregulation is at the core of H3K27M-glioma tumorigenesis. Here, we identify the BRG1-BAF complex as a critical regulator of enhancer and transcription factor landscapes, which maintain H3K27M glioma in their progenitor state, precluding glial differentiation, and establish pharmacologic targeting of the BAF complex as a novel treatment strategy for pediatric H3K27M glioma. See related commentary by Beytagh and Weiss, p. 2730. See related article by Mo et al., p. 2906.
Indexed as
EpigenomeGliomaAnimalsDNA HelicasesHumansMammalsMutationNeoplastic Stem CellsNuclear ProteinsTranscription FactorsDNA HelicasesNuclear ProteinsSMARCA4 protein, humanTranscription Factors
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