Global hypo-methylation in a proportion of glioblastoma enriched for an astrocytic signature is associated with increased invasion and altered immune landscape

James Boot; Gabriel Rosser; Dailya Kancheva; Claire Vinel; Yau Mun Lim; Nicola Pomella; Xinyu Zhang; Loredana Guglielmi; Denise Sheer; Michael Barnes; Sebastian Brandner; Sven Nelander; Kiavash Movahedi; Silvia Marino

doi:10.7554/eLife.77335

Global hypo-methylation in a proportion of glioblastoma enriched for an astrocytic signature is associated with increased invasion and altered immune landscape

James Boot, Gabriel Rosser, Dailya Kancheva, Claire Vinel, Yau Mun Lim, Nicola Pomella, Xinyu Zhang, Loredana Guglielmi, Denise Sheer, Michael Barnes, Sebastian Brandner, Sven Nelander, Kiavash Movahedi, Silvia Marino

Research output: Contribution to journal › Article › peer-review

7 Citations (Scopus)

Abstract

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 shareontogeny 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.

Original language	English
Article number	e77335
Number of pages	33
Journal	eLife
Volume	11
DOIs	https://doi.org/10.7554/eLife.77335
Publication status	Published - 22 Nov 2022

Bibliographical note

Funding Information:
This work is funded by grants from Brain Tumour Research (Centre of Excellence award to SM), Cancer Research UK (C23985/A29199 programme award to SM), Barts Charity (MGU0447 programme grant to SM). Part of the study was funded by the National Institute for Health Research to UCLH Biomedical research centre (BRC399/NS/RB/101410 to SB). SB is also supported by the Department of Health’s NIHR Biomedical Research Centre’s funding scheme. We acknowledge the use of data generated by the TCGA Research Network: https://www.cancer.gov/tcga.

Publisher Copyright:
© 2022, eLife Sciences Publications Ltd. All rights reserved.

Copyright:
Copyright 2023 Elsevier B.V., All rights reserved.

Keywords

Humans
Adult
Glioblastoma/pathology
Brain Neoplasms/genetics
Astrocytes/metabolism
DNA Methylation
Epigenomics

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10.7554/eLife.77335

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Boot, J., Rosser, G., Kancheva, D., Vinel, C., Lim, Y. M., Pomella, N., Zhang, X., Guglielmi, L., Sheer, D., Barnes, M., Brandner, S., Nelander, S., Movahedi, K., & Marino, S. (2022). Global hypo-methylation in a proportion of glioblastoma enriched for an astrocytic signature is associated with increased invasion and altered immune landscape. eLife, 11, Article e77335. https://doi.org/10.7554/eLife.77335

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title = "Global hypo-methylation in a proportion of glioblastoma enriched for an astrocytic signature is associated with increased invasion and altered immune landscape",

abstract = "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 shareontogeny 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.",

keywords = "Humans, Adult, Glioblastoma/pathology, Brain Neoplasms/genetics, Astrocytes/metabolism, DNA Methylation, Epigenomics",

author = "James Boot and Gabriel Rosser and Dailya Kancheva and Claire Vinel and Lim, {Yau Mun} and Nicola Pomella and Xinyu Zhang and Loredana Guglielmi and Denise Sheer and Michael Barnes and Sebastian Brandner and Sven Nelander and Kiavash Movahedi and Silvia Marino",

note = "Funding Information: This work is funded by grants from Brain Tumour Research (Centre of Excellence award to SM), Cancer Research UK (C23985/A29199 programme award to SM), Barts Charity (MGU0447 programme grant to SM). Part of the study was funded by the National Institute for Health Research to UCLH Biomedical research centre (BRC399/NS/RB/101410 to SB). SB is also supported by the Department of Health{\textquoteright}s NIHR Biomedical Research Centre{\textquoteright}s funding scheme. We acknowledge the use of data generated by the TCGA Research Network: https://www.cancer.gov/tcga. Publisher Copyright: {\textcopyright} 2022, eLife Sciences Publications Ltd. All rights reserved. Copyright: Copyright 2023 Elsevier B.V., All rights reserved.",

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Boot, J, Rosser, G, Kancheva, D, Vinel, C, Lim, YM, Pomella, N, Zhang, X, Guglielmi, L, Sheer, D, Barnes, M, Brandner, S, Nelander, S, Movahedi, K & Marino, S 2022, 'Global hypo-methylation in a proportion of glioblastoma enriched for an astrocytic signature is associated with increased invasion and altered immune landscape', eLife, vol. 11, e77335. https://doi.org/10.7554/eLife.77335

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AU - Lim, Yau Mun

AU - Pomella, Nicola

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AU - Guglielmi, Loredana

AU - Sheer, Denise

AU - Barnes, Michael

AU - Brandner, Sebastian

AU - Nelander, Sven

AU - Movahedi, Kiavash

AU - Marino, Silvia

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N2 - 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 shareontogeny 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.

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 shareontogeny 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.

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Global hypo-methylation in a proportion of glioblastoma enriched for an astrocytic signature is associated with increased invasion and altered immune landscape

Abstract

Bibliographical note

Keywords

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