Richard Drexler, Robin Khatri, Thomas Sauvigny, Malte Mohme, Cecile L Maire, Alice Ryba, Yahya Zghaibeh, Lasse Dührsen, Amanda Salviano-Silva, Katrin Lamszus, Manfred Westphal, Jens Gempt, Annika K Wefers, Julia E Neumann, Helena Bode, Fabian Hausmann, Tobias B Huber, Stefan Bonn, Kerstin Jütten, Daniel Delev, Katharina J Weber, Patrick N Harter, Julia Onken, Peter Vajkoczy, David Capper, Benedikt Wiestler, Michael Weller, Berend Snijder, Alicia Buck, Tobias Weiss, Pauline C Göller, Felix Sahm, Joelle Aline Menstel, David Niklas Zimmer, Michael B Keough, Lijun Ni, Michelle Monje, Dana Silverbush, Volker Hovestadt, Mario L Suvà, Saritha Krishna, Shawn L Hervey-Jumper, Ulrich Schüller, Dieter H Heiland, Sonja Hänzelmann, Franz L Ricklefs
Neural-tumor interactions drive glioma growth as evidenced in preclinical models, but clinical validation is limited. We present an epigenetically defined neural signature of glioblastoma that independently predicts 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 a high abundance of malignant stemcell-like cells in high-neural glioblastoma, primarily of the neural lineage...
May 17, 2024: Nature Medicine