Evidence map›Paper›PMID 39232581›Full record

ArticleCancer cell2024

GABAergic neuronal lineage development determines clinically actionable targets in diffuse hemispheric glioma, H3G34-mutant.

Ilon Liu, Gustavo Alencastro Veiga Cruzeiro, Lynn Bjerke, Rebecca F Rogers, Yura Grabovska, Alexander Beck, Alan Mackay, Tara Barron, Olivia A Hack, Michael A Quezada and 61 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

40 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

71 authors.

Ilon LiuDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, MA 02215, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Neurology with Experimental Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin und Humboldt-Universität zu Berlin, 10117 Berlin, Germany; Berlin Institute of Health at Charité - Universitätsmedizin Berlin, BIH Biomedical Innovation Academy, BIH Charité Digital Clinician Scientist Program, 10117 Berlin, Germany.
Gustavo Alencastro Veiga CruzeiroDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, MA 02215, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Lynn BjerkeDivision of Molecular Pathology, The Institute of Cancer Research, Sutton, Surrey SM2 5 NG, UK.
Rebecca F RogersDivision of Molecular Pathology, The Institute of Cancer Research, Sutton, Surrey SM2 5 NG, UK.
Yura GrabovskaDivision of Molecular Pathology, The Institute of Cancer Research, Sutton, Surrey SM2 5 NG, UK.
Alexander BeckCenter for Neuropathology, Ludwig-Maximilians-University, 81377 Munich, Germany.
Alan MackayDivision of Molecular Pathology, The Institute of Cancer Research, Sutton, Surrey SM2 5 NG, UK.
Tara BarronDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
Olivia A HackDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, MA 02215, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Michael A QuezadaDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
Valeria MolinariDivision of Molecular Pathology, The Institute of Cancer Research, Sutton, Surrey SM2 5 NG, UK.
McKenzie L ShawDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, MA 02215, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Marta Perez-SomarribaChildren & Young People's Unit, Royal Marsden Hospital NHS Trust, Sutton, Surrey SM2 5 NG, UK.
Sara TemelsoDivision of Molecular Pathology, The Institute of Cancer Research, Sutton, Surrey SM2 5 NG, UK.
Florence RaynaudDivision of Cancer Therapeutics, The Institute of Cancer Research, London SW7 3RK, UK.
Ruth RuddleDivision of Cancer Therapeutics, The Institute of Cancer Research, London SW7 3RK, UK.
Eshini PanditharatnaDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, MA 02215, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Bernhard EnglingerDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, MA 02215, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria; Center for Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria.
Hafsa M MireDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, MA 02215, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Li JiangDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, MA 02215, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Andrezza NascimentoDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, MA 02215, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Jenna LaBelleDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, MA 02215, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Rebecca HaaseDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, MA 02215, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Jacob RozowskyDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, MA 02215, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Sina NeyaziDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, MA 02215, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Alicia-Christina BaumgartnerDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, MA 02215, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Sophia CastellaniDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, MA 02215, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Samantha E HoffmanDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, MA 02215, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Amy CameronLurie Family Imaging Center, Center for Biomedical Imaging in Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Murry MorrowLurie Family Imaging Center, Center for Biomedical Imaging in Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Quang-De NguyenLurie Family Imaging Center, Center for Biomedical Imaging in Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Giulia PericoliDepartment of Onco-haematology, Gene and Cell Therapy, Bambino Gesù Children's Hospital-IRCCS, 00165 Rome, Italy.
Sibylle MadlenerDepartment of Pediatrics and Adolescent Medicine, Comprehensive Center for Pediatrics and Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria.
Lisa MayrDepartment of Pediatrics and Adolescent Medicine, Comprehensive Center for Pediatrics and Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria.
Christian DorferDepartment of Neurosurgery, Medical University of Vienna, 1090 Vienna, Austria.
Rene GeyereggerClinical Cell Biology, Children's Cancer Research Institute (CCRI), Vienna 1090, Austria.
Christopher RotaDepartment of Neurobiology, Harvard Medical School, Boston, MA 02215, USA.
Gerda RickenDivision of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna 1090, Austria.
Keith L LigonBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02215, USA; Department of Pathology, Boston Children's Hospital, Boston, MA 02115, USA.
Sanda AlexandrescuDepartment of Pathology, Boston Children's Hospital, Boston, MA 02115, USA.
Rodrigo T CartaxoDepartment of Pediatrics, University of Michigan, Ann Arbor, MI 48109, USA.
Benison LauDepartment of Pediatrics, University of Michigan, Ann Arbor, MI 48109, USA.
Santhosh UphadhyayaDepartment of Pediatrics, University of Michigan, Ann Arbor, MI 48109, USA.
Carl KoschmannDepartment of Pediatrics, University of Michigan, Ann Arbor, MI 48109, USA.
Emelie BraunDivision of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, 17177 Stockholm, Sweden.
Miri Danan-GottholdDivision of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, 17177 Stockholm, Sweden.
Lijuan HuDivision of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, 17177 Stockholm, Sweden.
Kimberly SilettiDivision of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, 17177 Stockholm, Sweden.
Erik SundströmDivision of Neurodegeneration, Department of Neurobiology, Care Sciences and Society, Karolinska Institute, 17177 Stockholm, Sweden.
Rebecca HodgeAllen Institute for Brain Science, Seattle, WA 98109, USA.
Ed LeinAllen Institute for Brain Science, Seattle, WA 98109, USA.
Sameer AgnihotriDepartments of Neurosurgery and Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, USA.
David D EisenstatMurdoch Children's Research Institute, Department of Paediatrics, University of Melbourne, Parkville, VIC 3052, Australia.
Simon StapletonDepartment of Neurosurgery, St George's Hospital NHS Trust, London SW17 0QT, UK.
Andrew KingDepartment of Neuropathology, King's College Hospital NHS Trust, London SE5 9RS, UK.
Cristina BleilDepartment of Neurosurgery, King's College Hospital NHS Trust, London SE5 9RS, UK.
Angela MastronuzziDepartment of Onco-haematology, Gene and Cell Therapy, Bambino Gesù Children's Hospital-IRCCS, 00165 Rome, Italy.
Kristina A ColeDivision of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Angela J WaandersAnn & Robert H Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA.
Angel Montero CarcabosoLaboratory of Molecular Oncology, Hospital Sant Joan de Déu, 08950 Barcelona, Spain.
Ulrich SchüllerInstitute of Neuropathology, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.
Darren HargraveUniversity College London Great Ormond Street Institute for Child Health, London WC1N 1EH, UK.
Maria VinciDepartment of Onco-haematology, Gene and Cell Therapy, Bambino Gesù Children's Hospital-IRCCS, 00165 Rome, Italy.
Fernando CarcellerChildren & Young People's Unit, Royal Marsden Hospital NHS Trust, Sutton, Surrey SM2 5 NG, UK; Division of Clinical Studies, The Institute of Cancer Research, London SW7 3RK, UK.
Christine HaberlerDivision of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna 1090, Austria.
Irene SlavcDepartment of Pediatrics and Adolescent Medicine, Comprehensive Center for Pediatrics and Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria.
Sten LinnarssonDivision of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, 17177 Stockholm, Sweden.
Johannes GojoDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, MA 02215, USA; Department of Pediatrics and Adolescent Medicine, Comprehensive Center for Pediatrics and Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria.
Michelle MonjeDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford, CA, USA.
Chris JonesDivision of Molecular Pathology, The Institute of Cancer Research, Sutton, Surrey SM2 5 NG, UK. Electronic address: chris.jones@icr.ac.uk.
Mariella G FilbinDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, MA 02215, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Electronic address: mariella.filbin@childrens.harvard.edu.

Funding

Targeting the Vasular SystemP50CA165962 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI Tracy T Batchelor · 2013 to 2026
$33.5M
Medical Scientist Training ProgramT32GM144273 · NIGMS · HARVARD MEDICAL SCHOOL · PI David Shumway Jones, Jacqueline A. Lees · 2022 to 2026
$14.7M
How the 3D Architecture of the Brain Shapes Cancer Cell Fate DecisionsDP2NS127705 · NINDS · DANA-FARBER CANCER INST · PI FILBIN, MARIELLA GRUBER · 2021 to 2024
$2.7M
Cancer Neuroscience Training ProgramT32CA272386 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI Tracy T Batchelor, MICHAEL ELDON GREENBERG · 2023 to 2026
$2.1M
The 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
$1.9M
NCI NIH HHS P50 CA165962NCI NIH HHS T32 CA272386NIGMS NIH HHS T32 GM144273NINDS NIH HHS DP2 NS127705NINDS NIH HHS R01 NS119231
6 · The paper itself

Abstract

Diffuse hemispheric gliomas, H3G34R/V-mutant (DHG-H3G34), are lethal brain tumors lacking targeted therapies. They originate from interneuronal precursors; however, leveraging this origin for therapeutic insights remains unexplored. Here, we delineate a cellular hierarchy along the interneuron lineage development continuum, revealing that DHG-H3G34 mirror spatial patterns of progenitor streams surrounding interneuron nests, as seen during human brain development. Integrating these findings with genome-wide CRISPR-Cas9 screens identifies genes upregulated in interneuron lineage progenitors as major dependencies. Among these, CDK6 emerges as a targetable vulnerability: DHG-H3G34 tumor cells show enhanced sensitivity to CDK4/6 inhibitors and a CDK6-specific degrader, promoting a shift toward more mature interneuron-like states, reducing tumor growth, and prolonging xenograft survival. Notably, a patient with progressive DHG-H3G34 treated with a CDK4/6 inhibitor achieved 17 months of stable disease. This study underscores interneuronal progenitor-like states, organized in characteristic niches, as a distinct vulnerability in DHG-H3G34, highlighting CDK6 as a promising clinically actionable target.

Identifiers

PMID39232581
PMCPMC11865364

What Socratic holds

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Registered trials

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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 Socratic graph.