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Review
. 2024 May 3;26(Supplement_2):S92-S100.
doi: 10.1093/neuonc/noad164.

H3K27M mutant glioma: Disease definition and biological underpinnings

Amanda M Saratsis  1 , Truman Knowles  2 , Antonela Petrovic  3 , Javad Nazarian  4   5   6
Affiliations
Review

H3K27M mutant glioma: Disease definition and biological underpinnings

Amanda M Saratsis et al. Neuro Oncol. .

Abstract

High-grade glioma (HGG) is the most common cause of cancer death in children and the most common primary central nervous system tumor in adults. While pediatric HGG was once thought to be biologically similar to the adult form of disease, research has shown these malignancies to be significantly molecularly distinct, necessitating distinct approaches to their clinical management. However, emerging data have shown shared molecular events in pediatric and adult HGG including the histone H3K27M mutation. This somatic missense mutation occurs in genes encoding one of two isoforms of the Histone H3 protein, H3F3A (H3.3), or HIST1H3B (H3.1), and is detected in up to 80% of pediatric diffuse midline gliomas and in up to 60% of adult diffuse gliomas. Importantly, the H3K27M mutation is associated with poorer overall survival and response to therapy compared to patients with H3 wild-type tumors. Here, we review the clinical features and biological underpinnings of pediatric and adult H3K27M mutant glioma, offering a groundwork for understanding current research and clinical approaches for the care of patients suffering with this challenging disease.

Keywords: H3K27M; epigenetics; glioma; histone; mutant.

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Conflict of interest statement

A.S. is an independent contractor, clinical development, for Chimerix Inc. The remaining authors have no conflicts of interest to declare.

Figures

Graphical Abstract
Graphical Abstract
Figure 1.
Figure 1.
T2 Sagittal (left) and axial (right) MR images of the brain, revealing a diffuse midline glioma (DMG) in the pons, also known as diffuse intrinsic pontine glioma (DIPG, white arrows).
Figure 2.
Figure 2.
Postcontrast T1 axial (right) and coronal (left) MR images of the brain, revealing a circumscribed high-grade glioma spanning bilateral cerebral hemispheres (white arrows).
Figure 3.
Figure 3.
Major biological underpinnings and cell of origin in H3K27M mutant diffuse midline glioma. Unique epigenetic, immunological, and genetic alterations are observed in this disease entity, with their cumulative effect being an arrest of oligodendrocyte precursor cell differentiation to facilitate tumor cell formation, maintenance, and progression. Created with BioRender.com.
See this image and copyright information in PMC

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