McCornack Colin, Woodiwiss Timothy, Hardi Angela, Yano Hiroko, Kim Albert H
Medical Scientist Training Program, Washington University School of Medicine, St. Louis, MO, United States.
Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO, United States.
Front Oncol. 2023 May 2;13:1144184. doi: 10.3389/fonc.2023.1144184. eCollection 2023.
Glioblastoma (GBM) is the most common and lethal primary brain malignancy and is characterized by a high degree of intra and intertumor cellular heterogeneity, a starkly immunosuppressive tumor microenvironment, and nearly universal recurrence. The application of various genomic approaches has allowed us to understand the core molecular signatures, transcriptional states, and DNA methylation patterns that define GBM. Histone posttranslational modifications (PTMs) have been shown to influence oncogenesis in a variety of malignancies, including other forms of glioma, yet comparatively less effort has been placed on understanding the transcriptional impact and regulation of histone PTMs in the context of GBM. In this review we discuss work that investigates the role of histone acetylating and methylating enzymes in GBM pathogenesis, as well as the effects of targeted inhibition of these enzymes. We then synthesize broader genomic and epigenomic approaches to understand the influence of histone PTMs on chromatin architecture and transcription within GBM and finally, explore the limitations of current research in this field before proposing future directions for this area of research.
胶质母细胞瘤（GBM）是最常见且致命的原发性脑恶性肿瘤，其特征在于肿瘤内和肿瘤间细胞高度异质性、显著的免疫抑制性肿瘤微环境以及几乎普遍的复发。各种基因组学方法的应用使我们能够了解定义GBM的核心分子特征、转录状态和DNA甲基化模式。组蛋白翻译后修饰（PTM）已被证明会影响包括其他形式神经胶质瘤在内的多种恶性肿瘤的肿瘤发生，但在GBM背景下，人们对理解组蛋白PTM的转录影响和调控的关注相对较少。在本综述中，我们讨论了研究组蛋白乙酰化和甲基化酶在GBM发病机制中的作用以及靶向抑制这些酶的效果的工作。然后，我们综合更广泛的基因组学和表观基因组学方法，以了解组蛋白PTM对GBM染色质结构和转录的影响，最后，在提出该研究领域的未来方向之前，探讨当前该领域研究的局限性。
