Defining, distinguishing and detecting the contribution of heterogeneous methylation to cancer heterogeneity.
Defining, distinguishing and detecting the contribution of heterogeneous methylation to cancer heterogeneity.
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DOI：
10.1016/j.semcdb.2016.08.030
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发表时间：
2017-04
影响因子：
7.3
通讯作者：
Wang TH
中科院分区：
文献类型：
--
作者：
Pisanic TR 2nd;Athamanolap P;Wang TH
DNA 甲基化是表观遗传基因调控的基本手段，几乎发生在所有细胞类型中。在包括人类在内的许多高等生物中，它在细胞分化和细胞表型的稳态维持中发挥着至关重要的作用。 DNA甲基化的控制传统上被认为是一个高度协调的线性过程，其失调与包括癌症在内的许多病理学有关，它发生在肿瘤组织发展的早期，甚至之前。最近的实验证据表明，与流行的范式相反，甲基化模式实际上是通过不精确的动态过程维持的。这些过程通常会导致细胞之间随着年龄的增长而积累的微小随机差异。然而，包括癌症本身在内的各种因素可能导致细胞间甲基化模式的显着差异，即。甲基化异质性。分子生物学技术的进步才刚刚开始，让我们能够深入了解这种异质性如何影响克隆进化和整体癌症异质性。在当前的综述中，我们首先介绍如何建立和维持基础双峰甲基化组的教学概述。然后，我们概述了导致异质甲基化产生的一些因素，以及这种异质性如何导致基因沉默并影响癌症表型的发展。最后，我们强调当前可用的甲基化评估技术及其对异质甲基化研究的适用性。
DNA methylation is a fundamental means of epigenetic gene regulation that occurs in virtually all cell types. In many higher organisms, including humans, it plays vital roles in cell differentiation and homeostatic maintenance of cell phenotype. The control of DNA methylation has traditionally been attributed to a highly coordinated, linear process, whose dysregulation has been associated with numerous pathologies including cancer, where it occurs early in, and even prior to, the development of neoplastic tissues. Recent experimental evidence has demonstrated that, contrary to prevailing paradigms, methylation patterns are actually maintained through inexact, dynamic processes. These processes normally result in minor stochastic differences between cells that accumulate with age. However, various factors, including cancer itself, can lead to substantial differences in intercellular methylation patterns, viz. methylation heterogeneity. Advancements in molecular biology techniques are just now beginning allow insight into how this heterogeneity contributes to clonal evolution and overall cancer heterogeneity. In the current review, we begin by presenting a didactic overview of how the basal bimodal methylome is established and maintained. We then provide a synopsis of some of the factors that lead to the accrual of heterogeneous methylation and how this heterogeneity may lead to gene silencing and impact the development of cancerous phenotypes. Lastly, we highlight currently available methylation assessment techniques and their suitability to the study of heterogeneous methylation.
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影响因子：
4.5
作者：
Christensen BC;Houseman EA;Marsit CJ;Zheng S;Wrensch MR;Wiemels JL;Nelson HH;Karagas MR;Padbury JF;Bueno R;Sugarbaker DJ;Yeh RF;Wiencke JK;Kelsey KT
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2.7
作者：
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20.3
作者：
Chim, CS;Fung, TK;Kwong, YL
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影响因子：
11.4
作者：
BOYES, J;BIRD, A
通讯作者：
BIRD, A
影响因子：
17.1
作者：
Aryee MJ;Liu W;Engelmann JC;Nuhn P;Gurel M;Haffner MC;Esopi D;Irizarry RA;Getzenberg RH;Nelson WG;Luo J;Xu J;Isaacs WB;Bova GS;Yegnasubramanian S
通讯作者：
Yegnasubramanian S