ArticleNature communications2019
Mitogenic and progenitor gene programmes in single pilocytic astrocytoma cells.
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Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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51citing papers in PubMed
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51 citing papers in PubMed, 89 citations in OpenAlex.
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- Modeling pediatric low-grade glioma heterogeneity using human forebrain organoids.Molecular cancer · 2026Article
- Multimodal analysis of pediatric pilocytic astrocytomas reveals tumor location-associated cellular and transcriptional heterogeneity.Neuro-oncology · 2025Article
- OncogenicbioRxiv : the preprint server for biology · 2025Article
- Aberrant coupling of glutamate and tyrosine kinase receptors enables neuronal control of brain-tumor growth.Neuron · 2025Article
- Multi-pronged analysis of pediatric low-grade glioma and ganglioglioma reveals a unique tumor microenvironment associated with BRAF alterations.Brain pathology (Zurich, Switzerland) · 2025Article
- A spatial map of MAPK-activated immunosuppressive myeloid populations in pediatric low-grade glioma.Nature immunology · 2025Article
- In silico purification improves DNA methylation-based classification rates of pediatric low-grade gliomas.Acta neuropathologica · 2025Article
- Learning the cellular origins across cancers using single-cell chromatin landscapes.Nature communications · 2025Article
- Multi-omics dissection of MAPK-driven senescence unveils therapeutic vulnerabilities in KIAA1549::BRAF-fusion pediatric low-grade glioma models.Signal transduction and targeted therapy · 2025Article
- BRAF/MEK inhibition induces cell state transitions boosting immune checkpoint sensitivity in BRAFCell reports. Medicine · 2025Article
- A simplified preparation method for single-nucleus RNA-sequencing using long-term frozen brain tumor tissues.Scientific reports · 2025Article
- Human single cell RNA-sequencing reveals a targetable CD8Nature communications · 2024Article
- MOST wanted: navigating the MAPK-OIS-SASP-tumor microenvironment axis in primary pediatric low-grade glioma and preclinical models.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2024Review
- Pediatric glioma immune profiling identifies TIM3 as a therapeutic target in BRAF fusion pilocytic astrocytoma.The Journal of clinical investigation · 2024Article
- Associations in cell type-specific hydroxymethylation and transcriptional alterations of pediatric central nervous system tumors.Nature communications · 2024Article
- Identifying tumor type and cell type-specific gene expression alterations in pediatric central nervous system tumors.Nature communications · 2024Article
- Comprehensive Transcriptomic Profiling of Diverse Brain Tumor Types Uncovers Complex Structures of the Brain Tumor Microenvironment.Biomedicines · 2024Article
- Gliomas: a reflection of temporal gliogenic principles.Communications biology · 2024Review
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Authors and funding
31 authors at 6 institutions in 5 countries.
Zachary J ReitmanDepartment of Cancer Biology, Dana Farber Cancer Institute, Boston, MA, 02215, USA.
Brenton R PaolellaDepartment of Cancer Biology, Dana Farber Cancer Institute, Boston, MA, 02215, USA.ORCID http://orcid.org/0000-0003-3394-828X
Guillaume BergtholdHoffmann-La Roche, Product Development, Innovative Pediatric Oncology Drug Discovery, CH-4070, Basel, Switzerland.
Kristine PeltonDepartment of Oncologic Pathology, Dana Farber Cancer Institute, Boston, MA, 02215, USA.
Sarah BeckerDepartment of Oncologic Pathology, Dana Farber Cancer Institute, Boston, MA, 02215, USA.
Robert JonesDepartment of Oncologic Pathology, Dana Farber Cancer Institute, Boston, MA, 02215, USA.
Claire E SinaiDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, MA, 02215, USA.
Hayley MalkinDepartment of Cancer Biology, Dana Farber Cancer Institute, Boston, MA, 02215, USA.
Ying HuangDepartment of Oncologic Pathology, Dana Farber Cancer Institute, Boston, MA, 02215, USA.
Leslie GrimmetMolecular Biology Core Facilities, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
Zachary T HerbertMolecular Biology Core Facilities, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
Yu SunDepartment of Cancer Biology, Dana Farber Cancer Institute, Boston, MA, 02215, USA.
Jessica L WeatherbeeDepartment of Cancer Biology, Dana Farber Cancer Institute, Boston, MA, 02215, USA.
John A AlbertaDepartment of Cancer Biology, Dana Farber Cancer Institute, Boston, MA, 02215, USA.
John F DaleyDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
Orit Rozenblatt-RosenBroad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Alexandra L ConduratBroad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Kenin QianDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, MA, 02215, USA.
Prasidda KhadkaDepartment of Cancer Biology, Dana Farber Cancer Institute, Boston, MA, 02215, USA.
Rosalind A SegalDepartment of Cancer Biology, Dana Farber Cancer Institute, Boston, MA, 02215, USA.
Daphne Haas-KoganDepartment of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
Mariella G FilbinBroad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Mario L SuvaBroad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.ORCID http://orcid.org/0000-0001-9898-5351
Aviv RegevBroad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Charles D StilesDepartment of Cancer Biology, Dana Farber Cancer Institute, Boston, MA, 02215, USA.
Mark W KieranDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, MA, 02215, USA.
Liliana GoumnerovaDepartment of Neurosurgery, Boston Children's Hospital, Boston, MA, 02215, USA.ORCID http://orcid.org/0000-0002-2662-719X
Keith L LigonBroad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Alex K ShalekBroad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Pratiti BandopadhayayBroad Institute of MIT and Harvard, Cambridge, MA, 02142, USA. pratiti_bandopadhayay@dfci.harvard.edu.
Rameen BeroukhimDepartment of Cancer Biology, Dana Farber Cancer Institute, Boston, MA, 02215, USA. rameen_beroukhim@dfci.harvard.edu.ORCID http://orcid.org/0000-0001-6303-3609
Dana-Farber Cancer Institute · USBroad Institute · USDana-Farber/Boston Children's Cancer and Blood Disorders Center · USBoston Children's Hospital · USHarvard University · USRoche (Switzerland) · CH
Funding
Role of Negative Costimulation in Regulation of AutoimmunityP01AI039671 · NIAID · YALE UNIVERSITY · PI David A. Hafler · 1996 to 2026
$51.7MSystems investigation of vaccine responses in B cell depleted autoimmune patientsU19AI089992 · NIAID · YALE UNIVERSITY · PI Steven H. Kleinstein · 2010 to 2026
$50.4MTargeting the Vasular SystemP50CA165962 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI DAPHNE A. HAAS-KOGAN · 2013 to 2026
$33.5MCenter for Cell CircuitsRM1HG006193 · NHGRI · BROAD INSTITUTE, INC. · PI BLAINEY, PAUL CLARK, HACOHEN, NIR · 2016 to 2020
$14.9MNovel Biologic Therapies for GVHDR01HL095791 · NHLBI · SEATTLE CHILDREN'S HOSPITAL · PI KEAN, LESLIE S · 2010 to 2025
$13.3MQuantitative and functional characterization of therapeutic resistance in cancerU54CA217377 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI SHALEK, ALEX K · 2017 to 2021
$10.2MTherapeutic Opportunities for Pediatric AstrocytomaP01CA142536 · NCI · DANA-FARBER CANCER INST · PI HAHN, WILLIAM C. · 2011 to 2015
$7.9MGenetic evolution of glioblastomas during radiation and temozolomide therapyR01CA188228 · NCI · DANA-FARBER CANCER INST · PI BEROUKHIM, RAMEEN, CHAKRAVARTI, ARNAB · 2015 to 2025
$6.9MA systems biology approach to fingerprint HIV immune defense in Elite ControllersR01HL134539 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI YU, XU · 2016 to 2019
$3.3MT cells in HCV/HIV co-infectionR01DA046277 · NIDA · MASSACHUSETTS GENERAL HOSPITAL · PI LAUER, GEORG MICHAEL · 2018 to 2022
$3.2MMYB family alterations in pediatric gliomasR01CA215489 · NCI · DANA-FARBER CANCER INST · PI BEROUKHIM, RAMEEN, LIGON, KEITH LLOYD · 2017 to 2021
$2.8MPrecision Medicine For Pediatric Low-Grade GliomasR01NS091620 · NINDS · DANA-FARBER CANCER INST · PI HAAS-KOGAN, DAPHNE A., RESNICK, ADAM CAIN · 2015 to 2019
$2.6MNCI NIH HHS F32 CA180653NCI NIH HHS K99 CA201592NCI NIH HHS P01 CA142536NCI NIH HHS P50 CA165962NCI NIH HHS R00 CA201592NCI NIH HHS R01 CA188228NCI NIH HHS R01 CA215489NCI NIH HHS R01 CA219943NCI NIH HHS R33 CA202820NCI NIH HHS U54 CA217377NHGRI NIH HHS RM1 HG006193NHLBI NIH HHS R01 HL095791NHLBI NIH HHS R01 HL134539NIAID NIH HHS P01 AI039671NIAID NIH HHS R01 AI138546NIAID NIH HHS U19 AI089992NIAID NIH HHS U24 AI118672NIDA NIH HHS R01 DA046277NINDS NIH HHS R01 NS091620
Abstract
Pilocytic astrocytoma (PA), the most common childhood brain tumor, is a low-grade glioma with a single driver BRAF rearrangement. Here, we perform scRNAseq in six PAs using methods that enabled detection of the rearrangement. When compared to higher-grade gliomas, a strikingly higher proportion of the PA cancer cells exhibit a differentiated, astrocyte-like phenotype. A smaller proportion of cells exhibit a progenitor-like phenotype with evidence of proliferation. These express a mitogen-activated protein kinase (MAPK) programme that was absent from higher-grade gliomas. Immune cells, especially microglia, comprise 40% of all cells in the PAs and account for differences in bulk expression profiles between tumor locations and subtypes. These data indicate that MAPK signaling is restricted to relatively undifferentiated cancer cells in PA, with implications for investigational therapies directed at this pathway.
Indexed as
AnimalsAstrocytomaBrain NeoplasmsHumansMAP Kinase Signaling SystemMiceMicrogliaMitogen-Activated Protein KinasesNeural Stem CellsOligodendrogliaOncogene Proteins, FusionProto-Oncogene Proteins B-rafTumor Cells, CulturedBRAF-KIAA1549 fusion protein, humanBRAF protein, humanMitogen-Activated Protein KinasesOncogene Proteins, FusionProto-Oncogene Proteins B-raf
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