人类肿瘤中DNA甲基化的异常模式:肿瘤进展的潜在后果。

IF 3.5 Q1 DENTISTRY, ORAL SURGERY & MEDICINE
S B Baylin, M Makos, J J Wu, R W Yen, A de Bustros, P Vertino, B D Nelkin
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引用次数: 0

摘要

DNA甲基化的不平衡,包括广泛的低甲基化、局部高甲基化和细胞甲基化能力的增加,是人类肿瘤的特征。这种不平衡始于肿瘤前细胞,并在肿瘤进展的后续阶段变得更加广泛。在正常细胞中,DNA甲基化的一个主要功能可能是调节DNA的区隔化,以确保转录活性染色质的区域复制早于大量转录非活性染色质。我们认为,在肿瘤进展过程中观察到的甲基化模式的改变,特别是区域高甲基化,可能标志着——甚至有助于建立——染色质组织的异常。反过来,这些染色质结构的变化可能通过基因的直接转录失活、突变易感性和等位基因缺失介导与肿瘤发展相关的基因表达的逐渐丧失。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Abnormal patterns of DNA methylation in human neoplasia: potential consequences for tumor progression.

An imbalance of DNA methylation, involving widespread hypomethylation, regional hypermethylation and increased cellular capacity for methylation, is characteristic of human neoplasia. This imbalance begins in preneoplastic cells and becomes more extensive throughout subsequent stages of tumor progression. In normal cells, a primary function of DNA methylation may be to modulate compartmentalization of DNA to ensure that regional areas of transcriptionally active chromatin replicate earlier than the bulk transcriptionally inactive chromatin. We argue here that the altered methylation patterns observed during tumor progression, especially regional hypermethylation, may mark--or even help to establish--abnormalities of chromatin organization. In turn, these changes in chromatin structure may, through direct transcriptional inactivation of genes, predisposition to mutations, and allelic deletions, mediate the progressive losses of gene expression associated with tumor development.

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