Fields of aberrant CpG island hypermethylation in Barrett's esophagus and associated adenocarcinoma.
Fields of aberrant CpG island hypermethylation in Barrett's esophagus and associated adenocarcinoma.
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发表时间：
2000-09
期刊：
影响因子：
11.2
通讯作者：
Cindy A. Eads;R. Lord;S. K. Kurumboor;K. Wickramasinghe;Margaret L. Skinner;T. Long;J. Peters;T. Demeester;K. Danenberg;P. Danenberg;P. Laird;K. Skinner
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作者：
Cindy A. Eads;R. Lord;S. K. Kurumboor;K. Wickramasinghe;Margaret L. Skinner;T. Long;J. Peters;T. Demeester;K. Danenberg;P. Danenberg;P. Laird;K. Skinner
食管腺癌（EAC）被认为是通过一个多阶段的过程，其中巴雷特化生通过低度和高度异型增生进展为浸润性癌症。在许多类型的人类癌症中已经观察到由启动子CpG岛超甲基化引起的肿瘤抑制基因的转录沉默。迄今为止，EAC中CpG岛超甲基化的分析仅限于CDKN 2A（p16）基因。在这项研究中，我们扩展了EAC的甲基化分析，包括其他三个基因，APC，CDH 1（E-cadherin）和ESR 1（ER，雌激素受体α），除了CDKN 2A。分子分析可以提供深入了解巴雷特食管和相关腺癌中不同组织学组织之间的复杂关系。因此，我们详细绘制了六例食管切除术病例中甲基化模式的空间分布。通过MethyLight技术分析了来自这6名患者的107份活检组织中4个CpG岛的超甲基化，共进行了428次甲基化分析。我们的研究结果表明，正常食管鳞状上皮是非甲基化的所有四个CpG岛。CDH 1在大多数其他组织类型中也未甲基化。ESR 1的高甲基化在炎性反流性食管炎和所有后续阶段中以高频率出现，而APC和CDKN 2A的高甲基化在Barrett化生、异型增生和EAC中发现。当它发生时，APC，CDKN 2A和ESR 1的高甲基化通常在一个大的连续区域中发现，这表明与化生相关的协调甲基化变化或异常高甲基化细胞的克隆扩增。
Esophageal adenocarcinoma (EAC) is thought to develop through a multistage process in which Barrett's metaplasia progresses through low- and high-grade dysplasia to invasive cancer. Transcriptional silencing of tumor suppressor genes by promoter CpG island hypermethylation has been observed in many types of human cancer. Analysis of CpG island hypermethylation in EAC has thus far been limited to the CDKN2A (p16) gene. In this study, we extend the methylation analysis of EAC to include three other genes, APC, CDH1 (E-cadherin), and ESR1 (ER, estrogen receptor alpha), in addition to CDKN2A. Molecular analysis can provide insight into the complex relationships between tissues with different histologies in Barrett's esophagus and associated adenocarcinoma. Therefore, we have mapped the spatial distribution of methylation patterns in six esophagectomy cases in detail. Hypermethylation of the four CpG islands was analyzed by the MethyLight technique in 107 biopsies derived from these six patients for a total of 428 methylation analyses. Our results show that normal esophageal squamous epithelium is unmethylated at all four CpG islands. CDH1 is unmethylated in most other tissue types as well. Hypermethylation of ESR1 is seen at high frequency in inflammatory reflux esophagitis and at all subsequent stages, whereas APC and CDKN2A hypermethylation is found in Barrett's metaplasia, dysplasia, and EAC. When it occurs, hypermethylation of APC, CDKN2A, and ESR1 is usually found in a large contiguous field, suggesting either a concerted methylation change associated with metaplasia or a clonal expansion of cells with abnormal hypermethylation.