Haase Santiago, Carney Stephen, Varela Maria Luisa, Mukherji Devarshi, Zhu Ziwen, Li Yingxiang, Nuñez Felipe J, Lowenstein Pedro R, Castro Maria G
Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Cell and Developmental Biology, Biomedical Science Research Building, Ann Arbor, MI 48109, USA; Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Biointerfaces Institute, BioInnovations in Brain Cancer Initiative (BIBC), University of Michigan, Ann Arbor, MI, 48109, USA.
Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Cell and Developmental Biology, Biomedical Science Research Building, Ann Arbor, MI 48109, USA; Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Biointerfaces Institute, BioInnovations in Brain Cancer Initiative (BIBC), University of Michigan, Ann Arbor, MI, 48109, USA.
Trends Cancer. 2024 Dec;10(12):1147-1160. doi: 10.1016/j.trecan.2024.09.007. Epub 2024 Oct 10.
Brain tumors in children and adults differ greatly in patient outcomes and responses to radiotherapy and chemotherapy. Moreover, the prevalence of recurrent mutations in histones and chromatin regulatory proteins in pediatric and young adult gliomas suggests that the chromatin landscape is rewired to support oncogenic programs. These early somatic mutations dysregulate widespread genomic loci by altering the distribution of histone post-translational modifications (PTMs) and, in consequence, causing changes in chromatin accessibility and in the histone code, leading to gene transcriptional changes. We review how distinct chromatin imbalances in glioma subtypes impact on oncogenic features such as cellular fate, proliferation, immune landscape, and radio resistance. Understanding these mechanisms of epigenetic dysregulation carries substantial implications for advancing targeted epigenetic therapies.
儿童和成人脑肿瘤在患者预后以及对放疗和化疗的反应方面存在很大差异。此外，小儿和年轻成人胶质瘤中组蛋白和染色质调节蛋白复发性突变的普遍性表明，染色质格局被重新布线以支持致癌程序。这些早期体细胞突变通过改变组蛋白翻译后修饰（PTM）的分布来失调广泛的基因组位点，进而导致染色质可及性和组蛋白编码发生变化，从而引起基因转录变化。我们综述了胶质瘤亚型中不同的染色质失衡如何影响致癌特征，如细胞命运、增殖、免疫格局和放射抗性。了解这些表观遗传失调机制对推进靶向表观遗传治疗具有重大意义。
