Chromatin mutations in pediatric high grade gliomas

Hsiao P J Voon; Lee H Wong

doi:10.3389/fonc.2022.1104129

Chromatin mutations in pediatric high grade gliomas

Front Oncol. 2023 Jan 6:12:1104129. doi: 10.3389/fonc.2022.1104129. eCollection 2022.

Authors

Hsiao P J Voon¹, Lee H Wong¹

Affiliation

¹ Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia.

Abstract

Pediatric high grade gliomas (HGG) are lethal tumors which are currently untreatable. A number of recent studies have provided much needed insights into the mutations and mechanisms which drive oncogenesis in pediatric HGGs. It is now clear that mutations in chromatin proteins, particularly H3.3 and its associated chaperone complex (ATRX), are a hallmark feature of pediatric HGGs. We review the current literature on the normal roles of the ATRX/H3.3 complex and how these functions are disrupted by oncogenic mutations. We discuss the current clinical trials and pre-clinical models that target chromatin and DNA, and how these agents fit into the ATRX/H3.3 mutation model. As chromatin mutations are a relatively new discovery in pediatric HGGs, developing clear mechanistic insights are a key step to improving therapies for these tumors.

Keywords: ATRX; DMG = diffuse midline glioma; H3.3 G34R/V; H3.3 K27M; KDM4; alternative lengthening of telomeres (ALT); histone H3.3; pediatric gliomas.

Publication types

Review