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Role of MacroH2A2 in the glioblastoma stem cell epigenome

Published online by Cambridge University Press:  05 September 2019

A Nikolic ,
K Ellestad ,
M Johnston ,
PB Dirks ,
FJ Zemp ,
C Gafiuk ,
DJ Mahoney  and
M Gallo
A Nikolic
Affiliation:
Alberta Children’s Health Research Institute (ACHRI), University of Calgary, Calgary, Alberta, Canada Charbonneau Cancer Institute, Calgary, AB, Canada Biochemistry and Molecular Biology
K Ellestad
Affiliation:
Alberta Children’s Health Research Institute (ACHRI), University of Calgary, Calgary, Alberta, Canada Charbonneau Cancer Institute, Calgary, AB, Canada
M Johnston
Affiliation:
Alberta Children’s Health Research Institute (ACHRI), University of Calgary, Calgary, Alberta, Canada Charbonneau Cancer Institute, Calgary, AB, Canada
PB Dirks
Affiliation:
Hospital for Sick Children, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada
FJ Zemp
Affiliation:
Alberta Children’s Health Research Institute (ACHRI), University of Calgary, Calgary, Alberta, Canada Biochemistry and Molecular Biology Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
C Gafiuk
Affiliation:
Alberta Children’s Health Research Institute (ACHRI), University of Calgary, Calgary, Alberta, Canada Biochemistry and Molecular Biology Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
DJ Mahoney
Affiliation:
Alberta Children’s Health Research Institute (ACHRI), University of Calgary, Calgary, Alberta, Canada Biochemistry and Molecular Biology Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
M Gallo
Affiliation:
Alberta Children’s Health Research Institute (ACHRI), University of Calgary, Calgary, Alberta, Canada Charbonneau Cancer Institute, Calgary, AB, Canada Biochemistry and Molecular Biology
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Abstract

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Glioblastoma is the most common primary malignant brain tumour in adults, and remains uniformly lethal. These tumours contain a subpopulation of glioblastoma stem cells (GSCs) that drive tumour recurrence and drug resistance. We find that MacroH2A2 is a histone variant that can stratify glioblastoma patients, with higher levels of this histone variant associated with better patient prognosis. Knockdown of macroH2A2 in GSCs is associated with increased self-renewal and an increased expression of stemness genes by RNA-seq. Our preliminary results suggest that macroH2A2 is a novel biomarker for glioblastoma and that macroH2A2 loss is a marker of GSC stemness and a poor prognostic marker in glioblastoma. This work identifies loss of macroH2A2 as a feature of GSCs and provides a framework for therapeutic modulation of this histone variant.

LEARNING OBJECTIVES

This presentation will enable the learner to:

  1. 1. Explain the role of epigenetics in glioblastoma pathophysiology

Type
Abstracts
Information
Canadian Journal of Neurological Sciences , Volume 46 , Supplement s2: ABSTRACT: 58th Annual Canadian Association of Neuropathologists Meeting , September 2019 , pp. S65
Copyright
© The Canadian Journal of Neurological Sciences Inc. 2019