Identification of driver and passenger DNA methylation in cancer by epigenomic analysis.

Identification of driver and passenger DNA methylation in cancer by epigenomic analysis.
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DOI:
10.1016/b978-0-12-380866-0.60010-1
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发表时间:
2010
影响因子:
--
通讯作者:
Pfeifer, Gerd P.
Pfeifer, Gerd P.
中科院分区:
生物学4区
文献类型:
--
作者:
Kalari, Satish;Pfeifer, Gerd P.

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人类癌症基因组的特点是 DNA 甲基化模式存在广泛的异常,包括大部分重复序列的 DNA 低甲基化和众多 CpG 岛的高甲基化。癌症中 DNA 甲基化模式的分析已从检查潜在重要候选基因的单基因研究发展到可以分析所有或几乎所有启动子和 CpG 岛序列的更全面的分析。我们简要概述了这些基因组规模的甲基化分析技术,总结了通过这些方法获得的一些信息,并讨论了我们在全基因组水平上对癌症甲基化畸变特异性的了解。现在的挑战是识别那些被认为对肿瘤发生、肿瘤进展或转移过程至关重要的甲基化变化,并将其与甲基化变化区分开来,甲基化变化只是伴随转化过程的过客事件,但本身对癌发生过程没有影响。
Human cancer genomes are characterized by widespread aberrations in DNA methylation patterns including DNA hypomethylation of mostly repetitive sequences and hypermethylation of numerous CpG islands. The analysis of DNA methylation patterns in cancer has progressed from single gene studies examining potentially important candidate genes to a more global analysis where all or almost all promoter and CpG island sequences can be analyzed. We provide a brief overview of these genome-scale methylation-profiling techniques, summarize some of the information that has been obtained with these approaches and discuss what we have learned about the specificity of methylation aberrations in cancer at a genome-wide level. The challenge is now to identify those methylation changes that are thought to be crucial for the processes of tumor initiation, tumor progression or metastasis and distinguish these from methylation changes that are merely passenger events that accompany the transformation process but have no effect per se on the process of carcinogenesis.