TY - JOUR TI - Global hypo-methylation in a proportion of glioblastoma enriched for an astrocytic signature is associated with increased invasion and altered immune landscape AU - Boot, James AU - Rosser, Gabriel AU - Kancheva, Dailya AU - Vinel, Claire AU - Lim, Yau Mun AU - Pomella, Nicola AU - Zhang, Xinyu AU - Guglielmi, Loredana AU - Sheer, Denise AU - Barnes, Michael AU - Brandner, Sebastian AU - Nelander, Sven AU - Movahedi, Kiavash AU - Marino, Silvia A2 - Lawler, Sean A2 - El-Deiry, Wafik S VL - 11 PY - 2022 DA - 2022/11/22 SP - e77335 C1 - eLife 2022;11:e77335 DO - 10.7554/eLife.77335 UR - https://doi.org/10.7554/eLife.77335 AB - 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. KW - glioblastoma KW - astrocytes KW - DNA methylation JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -