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Neuro Oncol2025;27(2):398-414.February 10, 2025Journal Article

EZH2 functional dichotomy in reactive oxygen species-stratified glioblastoma.

Lynnette Wei Hsien Koh1, Qing You Pang1, Wisna Novera1, See Wee Lim1, Yuk Kien Chong1, Jinyue Liu2, Samantha Ya Lyn Ang3,4, Ron Weng Yee Loh5, Huilin Shao6,7,8,9, Jianhong Ching10,11, Yulan Wang12, Stephen Yip13, Patrick Tan14,15,16,17, Shang Li14,17, David Chyi Yeu Low3,4, Anne Phelan18, Gabriel Rosser18, Nguan Soon Tan19,20, Carol Tang1,5,14, Beng Ti Ang1,3,4
1Neuro-Oncology Research Laboratory, Department of Research, National Neuroscience Institute, Singapore, Singapore.
2Laboratory of Single-Cell Spatial Neuromics, Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
3Department of Neurosurgery, National Neuroscience Institute, Singapore, Singapore.
4SingHealth Duke-NUS Neuroscience Academic Clinical Programme, Duke-National University of Singapore Medical School, Singapore, Singapore.
5Enabling Village, SG Enable, Singapore, Singapore.
6Institute for Health Innovation & Technology, National University of Singapore, Singapore, Singapore.
7Department of Biomedical Engineering, College of Design and Engineering, National University of Singapore, Singapore, Singapore.
8Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
9Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
10Cardiovascular & Metabolic Disorders Program, Duke-National University of Singapore Medical School, Singapore, Singapore.
11KK Research Centre, KK Women's and Children's Hospital, Singapore, Singapore.
12Singapore Phenome Centre, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
13Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, British Columbia, Canada.
14Cancer and Stem Cell Biology Program, Duke-National University of Singapore Medical School, Singapore, Singapore.
15Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
16Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
17Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
18BenevolentAI, London, UK.
19Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
20School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.
PubMed PMC DOI PDF

Abstract

BACKGROUND: Enhancer of zeste homolog 2 (EZH2), well known for its canonical methyltransferase activity in transcriptional repression in many cancers including glioblastoma (GBM), has an understudied noncanonical function critical for sustained tumor growth. Recent GBM consortial efforts reveal complex molecular heterogeneity for which therapeutic vulnerabilities correlated with subtype stratifica…

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