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表观遗传学在儿童癌症发病机制及耐药性中的作用。

Role of epigenetics in paediatric cancer pathogenesis & drug resistance.

作者信息

Leung Jia Yu, Chiu Hsin Yao, Taneja Reshma

机构信息

Department of Physiology, Healthy Longevity and NUS Centre for Cancer Research Translation Research Program, Yong Loo Lin School of Medicine, National University of Singapore (NUS), 2 Medical Drive, MD9, Singapore, 117593, Republic of Singapore.

Laboratory of NFκB Signalling, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, Proteos, Singapore, 138673, Republic of Singapore.

出版信息

Br J Cancer. 2025 May;132(9):757-769. doi: 10.1038/s41416-025-02961-2. Epub 2025 Mar 7.

Abstract

Paediatric oncogenesis is tightly intertwined with errors in developmental processes involving cell specification and differentiation, which are governed by intricate temporal epigenetic signals. As paediatric cancers are characterised by a low number of somatic mutations, dysregulated chromatin landscapes are believed to be key drivers of oncogenesis. Epigenetic dysregulation is induced by mutations and aberrant expression of histones and epigenetic regulatory genes, to altered DNA methylation patterns and dysregulated noncoding RNA expression. In this review, we discuss epigenetic alterations in paediatric cancer oncogenesis and recurrence, and their potential as diagnostic biomarkers. We also discuss various epigenetic drugs that have entered clinical trials for aggressive paediatric cancers. Targeting paediatric-specific epigenetic vulnerabilities may improve recurrence-free survival in high-risk cancers.

摘要

儿童肿瘤发生与涉及细胞特化和分化的发育过程中的错误紧密相连,这些过程由复杂的时间表观遗传信号调控。由于儿童癌症的特征是体细胞突变数量较少,染色质景观失调被认为是肿瘤发生的关键驱动因素。表观遗传失调是由组蛋白和表观遗传调控基因的突变及异常表达、DNA甲基化模式改变和非编码RNA表达失调引起的。在本综述中,我们讨论了儿童癌症发生和复发中的表观遗传改变及其作为诊断生物标志物的潜力。我们还讨论了已进入侵袭性儿童癌症临床试验的各种表观遗传药物。针对儿童特有的表观遗传脆弱性可能会提高高危癌症的无复发生存率。

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