Global hypo-methylation in a proportion of glioblastoma enriched for an astrocytic signature is associated with increased invasion and altered immune landscape
Division of Neuropathology, The National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, and Department of Neurodegenerative Disease, Queen Square, Institute of Neurology, University College London, London, United Kingdom
Nicola Pomella
Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University, London, United Kingdom
Xinyu Zhang
Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University, London, United Kingdom
Loredana Guglielmi
Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University, London, United Kingdom
Denise Sheer
Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University, London, United Kingdom
Michael Barnes
Centre for Translational Bioinformatics, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
Sebastian Brandner
Division of Neuropathology, The National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, and Department of Neurodegenerative Disease, Queen Square, Institute of Neurology, University College London, London, United Kingdom
We describe a subset of glioblastoma, the most prevalent malignant adult brain tumour, harbouring a bias towards hypomethylation at defined differentially methylated regions. This epigenetic signature correlates with an enrichment for an astrocytic gene signature, which together with the identification of enriched predicted binding sites of transcription factors known to cause demethylation and to be involved in astrocytic/glial lineage specification, point to a shared ontogeny between these glioblastomas and astroglial progenitors. At functional level, increased invasiveness, at least in part mediated by SRPX2, and macrophage infiltration characterise this subset of glioblastoma.
