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Review
. 2020 Sep 29;21(19):7193.
doi: 10.3390/ijms21197193.

Histone-Mutant Glioma: Molecular Mechanisms, Preclinical Models, and Implications for Therapy

Maya S Graham  1 , Ingo K Mellinghoff  1   2
Affiliations
Review

Histone-Mutant Glioma: Molecular Mechanisms, Preclinical Models, and Implications for Therapy

Maya S Graham et al. Int J Mol Sci. .

Abstract

Pediatric high-grade glioma (pHGG) is the leading cause of cancer death in children. Despite histologic similarities, it has recently become apparent that this disease is molecularly distinct from its adult counterpart. Specific hallmark oncogenic histone mutations within pediatric malignant gliomas divide these tumors into subgroups with different neuroanatomic and chronologic predilections. In this review, we will summarize the characteristic molecular alterations of pediatric high-grade gliomas, with a focus on how preclinical models of these alterations have furthered our understanding of their oncogenicity as well as their potential impact on developing targeted therapies for this devastating disease.

Keywords: H3K27M; diffuse midline glioma; oncohistone; pediatric high-grade glioma.

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Conflict of interest statement

I.K.M. has received research funding from General Electric, Agios, and Lilly and honoraria from Roche for a presentation. I.K.M. served in advisory roles for Agios, Amgen, Debiopharm, Novartis, Puma Biotechnology, and Voyager Therapeutics.

Figures

Figure 1
Figure 1
Oncoprint depicting tumor locations and selected typical genetic alterations in histone-mutant pHGG. Original data publicly available in PedcBioPortal.
Figure 2
Figure 2
Putative oncogenic mechanisms of H3K27M in pHGG.
Figure 3
Figure 3
Strategies for molecular intervention in oncohistone-driven pHGG. Ac: acetylation; ER: endoplasmic reticulum; Me: methylation; RNA pol II: RNA polymerase II. See text for other abbreviations common to multiple tables and figures.
See this image and copyright information in PMC

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