The epigenetics of cancer etiology

被引:229
作者
Feinberg, AP
机构
[1] Johns Hopkins Univ, Sch Med, Dept Med, Epigenet Unit, Baltimore, MD 21205 USA
[2] Johns Hopkins Univ, Sch Med, Dept Oncol, Epigenet Unit, Baltimore, MD 21205 USA
[3] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Epigenet Unit, Baltimore, MD 21205 USA
关键词
epigenetic dysregulation; Beckwith-Wiedemann syndrome; cancer etiology;
D O I
10.1016/j.semcancer.2004.06.005
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Epigenetic dysregulation is central to cancer development and progression. This dysregulation includes hypomethylation leading to oncogene activation and chromosomal instability, hypermethylation and tumor suppressor gene silencing, and chromatin modification acting directly, and cooperatively with methylation changes, to modify gene expression. In addition, disrupted genomic imprinting appears to contribute to colorectal cancer risk, and serves as a gatekeeper in Wilms tumor. A cancer predisposing disorder, Beckwith-Wiedemann syndrome, usually arises from epigenetic errors, solidifying the causal role of epigenetics in cancer. While cancer epigenetics has been reviewed extensively elsewhere, the main focus of this review will be to present the view that epigenetics and genetics are complementary in the area of cancer etiology, the focus of this volume. I propose a hypothesis in which epigenetic alterations contribute to tumor progression, but they also increase the probability that genetic changes, when they occur, will lead to cancer initiation. This hypothesis could contribute to a new understanding of the role of environmental carcinogens that may not be fully explained through a purely genetic view or by tests, such as bacterial mutation frequency, that ignore epigenefic factors. (C) 2004 Elsevier Ltd. All rights reserved.
引用
收藏
页码:427 / 432
页数:6
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