Dana Farber Cancer Institute, Boston, MA, USA.
The Hospital for Sick Children, Toronto, Canada.
J Neurooncol. 2020 Oct;150(1):27-34. doi: 10.1007/s11060-020-03553-1. Epub 2020 Aug 17.
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.
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.
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.
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.
通过发现组蛋白 3 尾部的新型突变，我们对弥漫性中线胶质瘤（DMG）生物学的认识，包括弥漫性内在脑桥胶质瘤，已经发生了革命性的变化，这导致了 2016 年对“弥漫性中线胶质瘤，H3 K27M 突变型”的重新分类。鉴于近年来提出了大量的基础、转化和临床信息，对弥漫性中线胶质瘤的表观遗传学进行综述是必要的。
通过在 PubMed 上搜索“弥漫性内在脑桥胶质瘤”、“脑桥胶质瘤”或“中线胶质瘤”等术语，对 1989 年至 2019 年发表的弥漫性中线胶质瘤表观遗传学文献进行了回顾。最终的参考文献列表是根据原创性和与我们综述的广泛范围的相关性生成的。
虽然 H3K27M 突变的影响了解得更好，但它表明在染色质景观和 DNA 修饰状态上有多种后果，这有助于 DMG 的进展。表观遗传修饰剂的转化发展迅速，已有几类抑制剂已进入临床试验测试。随着更多的药物在临床上可用，人们正在努力了解表观遗传修饰的靶向效应、肿瘤穿透和免疫微环境变化。
我们继续寻求对 DMG 中染色质失调和 DNA 修饰的调控机制的全面理解，同时我们也在进行表观遗传修饰剂的临床测试。从实验室到临床的坚定努力，以及协作的思维和统一的使命，最终将为 DMG 带来更好的结果。
