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表观遗传学在脑和脊髓肿瘤中的作用

The Role of Epigenetics in Brain and Spinal Cord Tumors.

作者信息

Park Sung-Hye

机构信息

Department of Pathology, College of Medicine, Seoul National University, Neuroscience Research Institute, 101 Daehak-ro, Jongno-gu, Seoul, Republic of Korea.

出版信息

Adv Exp Med Biol. 2023;1394:119-136. doi: 10.1007/978-3-031-14732-6_8.

Abstract

Identification of distinct genetic and epigenetic profiles in various neuroepithelial tumors has improved the classification and uncovered novel diagnostic, prognostic, and predictive molecular biomarkers for improved prediction of treatment response and outcome. Especially, in pediatric high-grade brain tumors, such as diffuse midline glioma, H3K27M-altered and posterior fossa group A-ependymoma, epigenetic changes predominate, along with changes in expression of known oncogenes and tumor suppressor genes induced by histone modifications and DNA methylation. The precise role of epigenetic abnormalities is important for understanding tumorigenesis and the establishment of brain tumor treatment strategies. Using powerful epigenetic-based therapies for cancer cells, the aberrantly regulated epigenome can be restored to a more normal state through epigenetic reprogramming. Combinations of agents targeting DNA methylation and/or other epigenetic modifications may be a promising cancer treatment. Therefore, the integration of multi-omics data including epigenomics is now important for classifying primary brain tumors and predicting their biological behavior. Recent advances in molecular genetics and epigenetic integrated diagnostics of brain tumors influence new strategies for targeted therapy.

摘要

对各种神经上皮肿瘤中不同遗传和表观遗传特征的识别,改进了分类方法,并发现了新的诊断、预后和预测分子生物标志物,以更好地预测治疗反应和结果。特别是在儿童高级别脑肿瘤中,如弥漫性中线胶质瘤、H3K27M改变的肿瘤和后颅窝A组室管膜瘤,表观遗传变化占主导地位,同时还有由组蛋白修饰和DNA甲基化诱导的已知癌基因和肿瘤抑制基因表达的变化。表观遗传异常的确切作用对于理解肿瘤发生和制定脑肿瘤治疗策略很重要。使用针对癌细胞的强大表观遗传疗法,可以通过表观遗传重编程将异常调节的表观基因组恢复到更正常的状态。靶向DNA甲基化和/或其他表观遗传修饰的药物组合可能是一种有前景的癌症治疗方法。因此,整合包括表观基因组学在内的多组学数据对于原发性脑肿瘤的分类和预测其生物学行为现在很重要。脑肿瘤分子遗传学和表观遗传综合诊断的最新进展影响了靶向治疗的新策略。

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