Methylation detection oligonucleotide microarray analysis: a high-resolution method for detection of CpG island methylation.

Methylation detection oligonucleotide microarray analysis: a high-resolution method for detection of CpG island methylation.
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DOI:
10.1093/nar/gkp413
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发表时间:
2009-07
影响因子:
14.9
通讯作者:
Lucito R
Lucito R
中科院分区:
生物学2区
文献类型:
--
作者:
Kamalakaran S;Kendall J;Zhao X;Tang C;Khan S;Ravi K;Auletta T;Riggs M;Wang Y;Helland A;Naume B;Dimitrova N;Børresen-Dale AL;Hicks J;Lucito R

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与基因相关的CpG岛的甲基化可以影响近端基因的表达,而非相关的CpG岛的甲基化与基因组的不稳定性相关。这种表观遗传修饰已被证明在许多病理中都很重要,从发育和疾病到癌症。我们报告了一种新型高分辨率微阵列的开发,该芯片可检测人类基因组中超过25,000个CpG岛的甲基化状态。实验表明,该方法具有较低的系统噪声,阵列探头具有较高的信噪比。不同细胞系之间的甲基化测量验证了测量的准确性。然后,我们在一组乳腺和卵巢肿瘤中发现了与基因启动子相关的CpG岛和与非启动子相关的CpG岛的变化。我们证明这种方法可以准确地识别癌症中的甲基化谱,原则上它可以区分任何CpG甲基化改变,并且可以适应于分析其他物种。
Methylation of CpG islands associated with genes can affect the expression of the proximal gene, and methylation of non-associated CpG islands correlates to genomic instability. This epigenetic modification has been shown to be important in many pathologies, from development and disease to cancer. We report the development of a novel high-resolution microarray that detects the methylation status of over 25 000 CpG islands in the human genome. Experiments were performed to demonstrate low system noise in the methodology and that the array probes have a high signal to noise ratio. Methylation measurements between different cell lines were validated demonstrating the accuracy of measurement. We then identified alterations in CpG islands, both those associated with gene promoters, as well as non-promoter-associated islands in a set of breast and ovarian tumors. We demonstrate that this methodology accurately identifies methylation profiles in cancer and in principle it can differentiate any CpG methylation alterations and can be adapted to analyze other species.
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