Genome-wide analysis of promoter methylation associated with gene expression profile in pancreatic adenocarcinoma.
Genome-wide analysis of promoter methylation associated with gene expression profile in pancreatic adenocarcinoma.
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DOI：
10.1158/1078-0432.ccr-10-3431
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发表时间：
2011-07-01
期刊：
影响因子：
--
通讯作者：
Goggins M
中科院分区：
文献类型：
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作者：
Vincent A;Omura N;Hong SM;Jaffe A;Eshleman J;Goggins M
本研究的目的是全面鉴定胰腺癌与正常胰腺之间的CpG岛甲基化改变以及相关的基因表达改变。
我们采用甲基化CpG岛扩增结合CpG岛微阵列技术（一种先前已验证其准确性和可重复性的方法），分析了9对胰腺癌与正常胰腺上皮组织以及3对来自同一个体的胰腺癌与淋巴组织中覆盖人类基因组21MB的27800个CpG岛的甲基化图谱。
该分析确定了1658个已知位点，这些位点在胰腺癌中与正常胰腺相比普遍存在差异甲基化。通过将胰腺DNA甲基化状态与相同样本在使用DNA甲基转移酶抑制剂5 - 氮杂 - 2′ - 脱氧胞苷和组蛋白去乙酰化酶抑制剂曲古抑菌素A处理前后的基因表达谱相结合，我们在胰腺癌中鉴定出了数十个异常甲基化和差异表达的基因，包括一份更全面的高甲基化和沉默基因列表，这些基因此前未被描述为癌症中异常甲基化的靶点。
我们期望异常高甲基化和沉默基因的鉴定将在诊断、预后和治疗方面具有应用价值。
The goal of this study was to comprehensively identify CpG island methylation alterations between pancreatic cancers and normal pancreata and their associated gene expression alterations. We employed Methylated CpG island Amplification followed by CpG island Microarray, a method previously validated for its accuracy and reproducibility, to analyze the methylation profile of 27800 CpG islands covering 21MB of the human genome in nine pairs of pancreatic cancer versus normal pancreatic epithelial tissues as well as in three matched pairs of pancreatic cancer versus lymphoid tissues from the same individual. This analysis identified 1658 known loci that were commonly differentially methylated in pancreatic cancer compared to normal pancreas. By integrating the pancreatic DNA methylation status with the gene expression profiles of the same samples before and after treatment with the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine, and the Histone Deacetylase inhibitor, Trichostatin A, we identified dozens of aberrantly methylated and differentially expressed genes in pancreatic cancers including a more comprehensive list of hypermethylated and silenced genes that have not been previously described as targets for aberrant methylation in cancer. We expect that the identification of aberrantly hypermethylated and silenced genes will have diagnostic, prognostic and therapeutic applications.