TY  - INPR
A1  - Drexler, Richard
A1  - Khatri, Robin
A1  - Sauvigny, Thomas
A1  - Mohme, Malte Eberhard
A1  - Maire, Cecile
A1  - Ryba, Alice
A1  - Zghaibeh, Yahya
A1  - Duhrsen, Lasse
A1  - Salviano-Silva, Amanda
A1  - Lamszus, Katrin
A1  - Westphal, Manfred
A1  - Gempt, Jens
A1  - Wefers, Annika K.
A1  - Neumann, Julia
A1  - Bode, Helena
A1  - Hausmann, Fabian
A1  - Huber, Tobias
A1  - Bonn, Stefan
A1  - Jütten, Kerstin Maria
A1  - Delev, Daniel I.
A1  - Weber, Katharina J.
A1  - Harter, Patrick Nikolaus
A1  - Onken, Julia Sophie
A1  - Vajkoczy, Peter
A1  - Capper, David
A1  - Wiestler, Benedikt
A1  - Weller, Michael
A1  - Snijder, Berend
A1  - Buck, Alicia
A1  - Weiss, Tobias
A1  - Keough, Michael B.
A1  - Ni, Lijun
A1  - Monje, Michelle
A1  - Silverbush, Dana
A1  - Hovestadt, Volker
A1  - Suva, Mario L.
A1  - Krishna, Saritha
A1  - Hervey-Jumper, Shawn
A1  - Schüller, Ulrich
A1  - Heiland, Henrik Dieter
A1  - Hänzelmann, Sonja
A1  - Ricklefs, Franz Lennard
T1  - Epigenetic neural glioblastoma enhances synaptic integration and predicts therapeutic vulnerability
T2  - bioRxiv
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.
Y1  - 2023
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/75092
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-750924
IS  - 2023.08.04.552017
ER  -