Epigenetic neural glioblastoma enhances synaptic integration and predicts therapeutic vulnerability.

BDNF DIPG DMG GBM Glioma NPC OPC cancer neuroscience connectivity neuron neuronal activity stem cell synapse

Journal

bioRxiv : the preprint server for biology
Titre abrégé: bioRxiv
Pays: United States
ID NLM: 101680187

Informations de publication

Date de publication:
07 Aug 2023
Historique:
pubmed: 23 8 2023
medline: 23 8 2023
entrez: 23 8 2023
Statut: epublish

Résumé

Neural-tumor interactions drive glioma growth as evidenced in preclinical models, but clinical validation is nascent. We present an epigenetically defined neural signature of glioblastoma that independently affects patients' survival. We use reference signatures of neural cells to deconvolve tumor DNA and classify samples into low- or high-neural tumors. High-neural glioblastomas exhibit hypomethylated CpG sites and upregulation of genes associated with synaptic integration. Single-cell transcriptomic analysis reveals high abundance of stem cell-like malignant cells classified as oligodendrocyte precursor and neural precursor cell-like in high-neural glioblastoma. High-neural glioblastoma cells engender neuron-to-glioma synapse formation

Identifiants

DOI: 10.1101/2023.08.04.552017 PMID: 37609137 PMC: PMC10441357
pubmed: 37609137
doi: 10.1101/2023.08.04.552017
pmc: PMC10441357
pii:
doi:

Types de publication

Preprint

Langues

eng

Subventions

Organisme : NCI NIH HHS
ID : U19 CA264504
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA258384
Pays : United States
Organisme : NINDS NIH HHS
ID : DP1 NS111132
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS092597
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA264339
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA097257
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA165962
Pays : United States
Organisme : NINDS NIH HHS
ID : K08 NS110919
Pays : United States

Déclaration de conflit d'intérêts

Competing Interests M.L.S. is equity holder, scientific co-founder and advisory board member of Immunitas Therapeutics. M.M. holds equity in MapLight Therapeutics.

Auteurs

Richard Drexler (R)

Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Department of Neurology, Stanford University, Stanford, CA, 94305, USA.

Robin Khatri (R)

Institute of Medical Systems Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Center for Biomedical AI, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Thomas Sauvigny (T)

Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Malte Mohme (M)

Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Cecile L Maire (CL)

Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Alice Ryba (A)

Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Yahya Zghaibeh (Y)

Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Lasse Dührsen (L)

Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Amanda Salviano-Silva (A)

Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Katrin Lamszus (K)

Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Manfred Westphal (M)

Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Jens Gempt (J)

Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Annika K Wefers (AK)

Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Mildred Scheel Cancer Career Center HaTriCS4, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Julia Neumann (J)

Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Department of Pediatric Hematology and Oncology, Research Institute Children's Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Research Institute Children's Cancer Center Hamburg, Hamburg, Germany.

Helena Bode (H)

Research Institute Children's Cancer Center Hamburg, Hamburg, Germany.

Fabian Hausmann (F)

Institute of Medical Systems Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Center for Biomedical AI, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Tobias B Huber (TB)

III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Hamburg Center for Translational Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Stefan Bonn (S)

Institute of Medical Systems Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Center for Biomedical AI, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Kerstin Jütten (K)

Department of Neurosurgery, University Hospital Aachen, Aachen, Germany.

Daniel Delev (D)

Department of Neurosurgery, University Hospital Aachen, Aachen, Germany.

Katharina J Weber (KJ)

Neurological Institute (Edinger Institute), University Hospital Frankfurt, Frankfurt am Main, Germany.
German Cancer Consortium (DKTK), Heidelberg, Germany and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Frankfurt Cancer Institute (FCI), Frankfurt am Main, Germany.
University Cancer Center (UCT) Frankfurt, Frankfurt am Main, Germany.

Patrick N Harter (PN)

Neurological Institute (Edinger Institute), University Hospital Frankfurt, Frankfurt am Main, Germany.
Institute of Neuropathology, Faculty of Medicine, LMU Munich, Munich, Germany.

Julia Onken (J)

Department of Neurosurgery, Charité - Universitätsmedizin Berlin, Berlin, Germany.

Peter Vajkoczy (P)

Department of Neurosurgery, Charité - Universitätsmedizin Berlin, Berlin, Germany.

David Capper (D)

Department of Neuropathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany.

Benedikt Wiestler (B)

Department of Neuroradiology, Klinikum rechts der Isar, School of Medicine, Technical University Munich, Munich.

Michael Weller (M)

Department of Neurology, Clinical Neuroscience Center, University Hospital Zurich, Switzerland. Department of Neurology, University of Zürich, Switzerland.

Berend Snijder (B)

Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.

Alicia Buck (A)

Department of Neurology, Clinical Neuroscience Center, University Hospital Zurich, Switzerland. Department of Neurology, University of Zürich, Switzerland.

Tobias Weiss (T)

Department of Neurology, Clinical Neuroscience Center, University Hospital Zurich, Switzerland. Department of Neurology, University of Zürich, Switzerland.

Michael B Keough (MB)

Department of Neurology, Stanford University, Stanford, CA, 94305, USA.

Lijun Ni (L)

Department of Neurology, Stanford University, Stanford, CA, 94305, USA.

Michelle Monje (M)

Department of Neurology, Stanford University, Stanford, CA, 94305, USA.

Dana Silverbush (D)

Broad Institute of Harvard and MIT, Cambridge, MA, USA.

Volker Hovestadt (V)

Broad Institute of Harvard and MIT, Cambridge, MA, USA.

Mario L Suvà (ML)

Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.

Saritha Krishna (S)

Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, 94143, USA.

Shawn L Hervey-Jumper (SL)

Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, 94143, USA.

Ulrich Schüller (U)

Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Department of Pediatric Hematology and Oncology, Research Institute Children's Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Research Institute Children's Cancer Center Hamburg, Hamburg, Germany.

Dieter H Heiland (DH)

Department of Neurosurgery, Medical Center University of Freiburg, Freiburg, Germany.

Sonja Hänzelmann (S)

Institute of Medical Systems Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Center for Biomedical AI, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Hamburg Center for Translational Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Franz L Ricklefs (FL)

Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Classifications MeSH