Department of Chemical and Biomolecular Engineering, Rice University, Houston, TX, 77005, USA.
Department of Pediatrics, Division of Hematology and Oncology, Baylor College of Medicine, Texas Children's Hospital, Dan L. Duncan Cancer Center, Houston, TX, 77030, USA.
Neuropathol Appl Neurobiol. 2020 Feb;46(1):48-56. doi: 10.1111/nan.12612. Epub 2020 Mar 24.
Genetic alterations identified across several paediatric and adult brain tumours reveal recurrent disruption of active chromatin landscapes and dysregulation of transcriptional programmes. Noncoding elements, specifically enhancers, are central to these mechanisms, and are influenced by developmental and neural gene regulatory signatures. Epigenomic and transcriptomic methods and techniques have facilitated detection of active enhancers, and characterization of brain tumours integrated with genomic structural information. These datasets have provided new insights into the mechanisms of transcriptional control that are profoundly altered in childhood and adult brain cancer; offering new ideas and molecular targets for therapeutic intervention. This review summarizes recent advances in our understanding of active transcriptional programmes of brain cancer, their impact on tumour development, and research areas for further exploration.
在几种儿科和成人脑肿瘤中鉴定的遗传改变揭示了活性染色质景观的反复破坏和转录程序的失调。非编码元件,特别是增强子,是这些机制的核心,受发育和神经基因调控特征的影响。表观基因组学和转录组学方法和技术促进了活性增强子的检测,并对与基因组结构信息整合的脑肿瘤进行了表征。这些数据集为转录控制机制提供了新的见解,这些机制在儿童和成人脑癌中发生了深刻的改变;为治疗干预提供了新的思路和分子靶点。这篇综述总结了我们对脑癌活性转录程序的理解的最新进展,及其对肿瘤发展的影响,以及进一步探索的研究领域。