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Epigenetic neural glioblastoma enhances synaptic integration and predicts therapeutic vulnerability

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Epigenetic neural glioblastoma enhances synaptic integration and predicts therapeutic vulnerability. / Drexler, Richard; Khatri, Robin; Sauvigny, Thomas; Mohme, Malte; Maire, Cecile L; Ryba, Alice; Zghaibeh, Yahya; Dührsen, Lasse; Salviano-Silva, Amanda; Lamszus, Katrin; Westphal, Manfred; Gempt, Jens; Wefers, Annika K; Neumann, Julia; Bode, Helena; Hausmann, Fabian; Huber, Tobias B; Bonn, Stefan; Jütten, Kerstin; Delev, Daniel; Weber, Katharina J; Harter, Patrick N; Onken, Julia; Vajkoczy, Peter; Capper, David; Wiestler, Benedikt; Weller, Michael; Snijder, Berend; Buck, Alicia; Weiss, Tobias; Keough, Michael B; Ni, Lijun; Monje, Michelle; Silverbush, Dana; Hovestadt, Volker; Suvà, Mario L; Krishna, Saritha; Hervey-Jumper, Shawn L; Schüller, Ulrich; Heiland, Dieter H; Hänzelmann, Sonja; Ricklefs, Franz L.

in: bioRxiv, 07.08.2023.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › Preprint › Forschung

Harvard

Drexler, R, Khatri, R, Sauvigny, T, Mohme, M, Maire, CL, Ryba, A, Zghaibeh, Y, Dührsen, L, Salviano-Silva, A, Lamszus, K, Westphal, M, Gempt, J, Wefers, AK, Neumann, J, Bode, H, Hausmann, F, Huber, TB, Bonn, S, Jütten, K, Delev, D, Weber, KJ, Harter, PN, Onken, J, Vajkoczy, P, Capper, D, Wiestler, B, Weller, M, Snijder, B, Buck, A, Weiss, T, Keough, MB, Ni, L, Monje, M, Silverbush, D, Hovestadt, V, Suvà, ML, Krishna, S, Hervey-Jumper, SL, Schüller, U, Heiland, DH, Hänzelmann, S & Ricklefs, FL 2023, 'Epigenetic neural glioblastoma enhances synaptic integration and predicts therapeutic vulnerability', bioRxiv. https://doi.org/10.1101/2023.08.04.552017

APA

Drexler, R., Khatri, R., Sauvigny, T., Mohme, M., Maire, C. L., Ryba, A., Zghaibeh, Y., Dührsen, L., Salviano-Silva, A., Lamszus, K., Westphal, M., Gempt, J., Wefers, A. K., Neumann, J., Bode, H., Hausmann, F., Huber, T. B., Bonn, S., Jütten, K., ... Ricklefs, F. L. (2023). Epigenetic neural glioblastoma enhances synaptic integration and predicts therapeutic vulnerability. bioRxiv. https://doi.org/10.1101/2023.08.04.552017

Vancouver

Drexler R, Khatri R, Sauvigny T, Mohme M, Maire CL, Ryba A et al. Epigenetic neural glioblastoma enhances synaptic integration and predicts therapeutic vulnerability. bioRxiv. 2023 Aug 7. https://doi.org/10.1101/2023.08.04.552017

Bibtex

@article{fb811fd4d2b44cf88590dbc361a49d85,
title = "Epigenetic neural glioblastoma enhances synaptic integration and predicts therapeutic vulnerability",
abstract = "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 in vitro and in vivo and show an unfavorable survival after xenografting. In patients, a high-neural signature associates with decreased survival as well as increased functional connectivity and can be detected via DNA analytes and brain-derived neurotrophic factor in plasma. Our study presents an epigenetically defined malignant neural signature in high-grade gliomas that is prognostically relevant.",
author = "Richard Drexler and Robin Khatri and Thomas Sauvigny and Malte Mohme and Maire, {Cecile L} and Alice Ryba and Yahya Zghaibeh and Lasse D{\"u}hrsen and Amanda Salviano-Silva and Katrin Lamszus and Manfred Westphal and Jens Gempt and Wefers, {Annika K} and Julia Neumann and Helena Bode and Fabian Hausmann and Huber, {Tobias B} and Stefan Bonn and Kerstin J{\"u}tten and Daniel Delev and Weber, {Katharina J} and Harter, {Patrick N} and Julia Onken and Peter Vajkoczy and David Capper and Benedikt Wiestler and Michael Weller and Berend Snijder and Alicia Buck and Tobias Weiss and Keough, {Michael B} and Lijun Ni and Michelle Monje and Dana Silverbush and Volker Hovestadt and Suv{\`a}, {Mario L} and Saritha Krishna and Hervey-Jumper, {Shawn L} and Ulrich Sch{\"u}ller and Heiland, {Dieter H} and Sonja H{\"a}nzelmann and Ricklefs, {Franz L}",
year = "2023",
month = aug,
day = "7",
doi = "10.1101/2023.08.04.552017",
language = "English",
journal = "bioRxiv",
issn = "2692-8205",

}

RIS

TY - JOUR

T1 - Epigenetic neural glioblastoma enhances synaptic integration and predicts therapeutic vulnerability

AU - Drexler, Richard

AU - Khatri, Robin

AU - Sauvigny, Thomas

AU - Mohme, Malte

AU - Maire, Cecile L

AU - Ryba, Alice

AU - Zghaibeh, Yahya

AU - Dührsen, Lasse

AU - Salviano-Silva, Amanda

AU - Lamszus, Katrin

AU - Westphal, Manfred

AU - Gempt, Jens

AU - Wefers, Annika K

AU - Neumann, Julia

AU - Bode, Helena

AU - Hausmann, Fabian

AU - Huber, Tobias B

AU - Bonn, Stefan

AU - Jütten, Kerstin

AU - Delev, Daniel

AU - Weber, Katharina J

AU - Harter, Patrick N

AU - Onken, Julia

AU - Vajkoczy, Peter

AU - Capper, David

AU - Wiestler, Benedikt

AU - Weller, Michael

AU - Snijder, Berend

AU - Buck, Alicia

AU - Weiss, Tobias

AU - Keough, Michael B

AU - Ni, Lijun

AU - Monje, Michelle

AU - Silverbush, Dana

AU - Hovestadt, Volker

AU - Suvà, Mario L

AU - Krishna, Saritha

AU - Hervey-Jumper, Shawn L

AU - Schüller, Ulrich

AU - Heiland, Dieter H

AU - Hänzelmann, Sonja

AU - Ricklefs, Franz L

PY - 2023/8/7

Y1 - 2023/8/7

N2 - 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 in vitro and in vivo and show an unfavorable survival after xenografting. In patients, a high-neural signature associates with decreased survival as well as increased functional connectivity and can be detected via DNA analytes and brain-derived neurotrophic factor in plasma. Our study presents an epigenetically defined malignant neural signature in high-grade gliomas that is prognostically relevant.

AB - 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 in vitro and in vivo and show an unfavorable survival after xenografting. In patients, a high-neural signature associates with decreased survival as well as increased functional connectivity and can be detected via DNA analytes and brain-derived neurotrophic factor in plasma. Our study presents an epigenetically defined malignant neural signature in high-grade gliomas that is prognostically relevant.

U2 - 10.1101/2023.08.04.552017

DO - 10.1101/2023.08.04.552017

M3 - Preprint

C2 - 37609137

JO - bioRxiv

JF - bioRxiv

SN - 2692-8205

ER -