The role of aberrant DNA methylation in cancer initiation and clinical impacts.
The role of aberrant DNA methylation in cancer initiation and clinical impacts.
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异常DNA甲基化在癌症开始和临床影响中的作用。
DOI：
10.1177/17588359231220511
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发表时间：
2024
影响因子：
4.9
通讯作者：
J. Wakefield, Matthew
中科院分区：
文献类型：
--
作者：
Geissler, Franziska;Nesic, Ksenija;Kondrashova, Olga;Dobrovic, Alexander;Swisher, Elizabeth M.;Scott, Clare L.;J. Wakefield, Matthew
关键词：
表观遗传学改变，包括异常的DNA甲基化，现在被认为是癌症的真实特征，它可以促进癌症的发生、发展、治疗反应和治疗抵抗。基因启动子的甲基化可以对癌症风险、临床分层和治疗结果产生一系列影响。我们提供了几个重要的基因例子，这些基因可以被启动子甲基化沉默或激活，并强调了它们的临床意义。这些基因包括错配DNA修复基因MLH1和MSH2，同源重组DNA修复基因BRCA1和RAD51C，TERT癌基因和P15/P16/RB1/E2F抑癌轴基因。我们还讨论了这些甲基化改变最初是如何发生的--无论是在CpG岛甲基化表型的背景下还是在构成DNA甲基化的背景下。用来测量甲基化的检测方法的选择对甲基化状态的解释有重要的影响，并提供了一些影响临床决策的例子。循环肿瘤DNA(CtDNA)中的异常DNA甲基化模式在使用液体活检进行非侵入性癌症检测和监测方面也显示出巨大的前景；然而，在可能存在结构性甲基化的情况下解释这些结果时必须谨慎。因此，这篇综述旨在为研究人员和临床医生提供对这一广泛而重要的主题的全面总结，说明评估癌症中异常DNA甲基化的潜力和陷阱。沉默基因在癌症的启动和临床影响中的作用基因可以通过在其上放置分子标签来沉默。这是一个正常的过程，它控制着何时何地可以使用基因。在某些情况下，这种沉默可能被错误地应用于参与预防癌症、导致癌症启动和进展的基因。这篇综述讨论了这些标记过程之一的作用，DNA甲基化及其在癌症发生和治疗中的作用。
Epigenetic alterations, including aberrant DNA methylation, are now recognized as bone fide hallmarks of cancer, which can contribute to cancer initiation, progression, therapy responses and therapy resistance. Methylation of gene promoters can have a range of impacts on cancer risk, clinical stratification and therapeutic outcomes. We provide several important examples of genes, which can be silenced or activated by promoter methylation and highlight their clinical implications. These include the mismatch DNA repair genes MLH1 and MSH2, homologous recombination DNA repair genes BRCA1 and RAD51C, the TERT oncogene and genes within the P15/P16/RB1/E2F tumour suppressor axis. We also discuss how these methylation changes might occur in the first place – whether in the context of the CpG island methylator phenotype or constitutional DNA methylation. The choice of assay used to measure methylation can have a significant impact on interpretation of methylation states, and some examples where this can influence clinical decision-making are presented. Aberrant DNA methylation patterns in circulating tumour DNA (ctDNA) are also showing great promise in the context of non-invasive cancer detection and monitoring using liquid biopsies; however, caution must be taken in interpreting these results in cases where constitutional methylation may be present. Thus, this review aims to provide researchers and clinicians with a comprehensive summary of this broad, but important subject, illustrating the potentials and pitfalls of assessing aberrant DNA methylation in cancer. Silencing genes role in initiation of cancer and clinical impacts Genes can be silenced by molecular tags being placed on them. This is a normal process that controls when and where genes are available to be used. In some cases this silencing can be incorrectly applied to genes involved in preventing cancer, causing cancer initiation and progression. This review discusses the role of one of these tagging processes, DNA methylation and its role in initiation of cancer and implications for treatment.
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影响因子：
19
作者：
Ceccaldi R;Rondinelli B;D'Andrea AD
通讯作者：
D'Andrea AD
影响因子：
5.7
作者：
Apolonio, Joana Dias;Dias, Joao S.;Fernandes, Monica Teotonio;Komosa, Martin;Lipman, Tatiana;Zhang, Cindy H.;Leao, Ricardo;Lee, Donghyun;Nunes, Nuno Miguel;Maia, Ana-Teresa;Morera, Jose L.;Vicioso, Luis;Tabori, Uri;Castelo-Branco, Pedro
通讯作者：
Castelo-Branco, Pedro
影响因子：
8.8
作者：
Deng, G;Peng, E;Gum, J;Terdiman, J;Sleisenger, M;Kim, Y S
通讯作者：
Kim, Y S
影响因子：
3.8
作者：
CHAN, KK;GIANNINI, DD;SADEE, W
通讯作者：
SADEE, W
影响因子：
5.7
作者：
Takeshima H;Yoda Y;Wakabayashi M;Hattori N;Yamashita S;Ushijima T
通讯作者：
Ushijima T