Diffuse midline glioma: review of epigenetics

Abstract

Purpose: Our understanding of diffuse midline glioma (DMG) biology inclusive of diffuse intrinsic pontine glioma has been revolutionized by the discovery of novel mutations on the tails of histone 3, leading to the reclassification in 2016 of 'diffuse midline glioma, H3 K27M-mutant.' Given the abundance of basic, translational, and clinical information put forth in recent years, a review of the epigenetics of diffuse midline glioma is warranted.

Methods: Literature for the epigenetics of diffuse midline glioma published from 1989 to 2019 was reviewed by searching PubMed using the terms "diffuse intrinsic pontine glioma", "pontine glioma", or "midline glioma". The final references list was generated on the basis of originality and relevance to the broad scope of our review.

Results: The effects of H3K27M-mutation, while better understood, suggest multiple consequences on the chromatin landscape and DNA modification states, contributed to the progression of DMG. A rapid pace of translational development is occurring for epigenetic modifiers, and several classes of inhibitors have already made their way into clinical trial testing. As more agents become clinically accessible, immense effort is underway to understand the target effects, tumor penetration, and immune microenvironmental changes of epigenetic modification.

Conclusion: We continue to seek a comprehensive understanding of the mechanisms that govern chromatin dysregulation and DNA modification in DMG, and in parallel we forge ahead with clinical testing of epigenetic modifiers. The determined efforts from bench to bedside, along with collaborative mindset and unified mission, will ultimately result in improved outcomes for DMG.

Keywords: Diffuse; Epigenetic(s); Glioma; H3K27M; Histone(s); Midline.