Progressive methylation during the serrated neoplasia pathway of the colorectum
Progressive methylation during the serrated neoplasia pathway of the colorectum
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DOI：
10.1038/modpathol.3800261
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发表时间：
2005-02-01
期刊：
影响因子：
7.5
通讯作者：
Kim, KM
中科院分区：
文献类型：
--
作者：
Dong, SM;Lee, EJ;Kim, KM
锯齿状腺瘤是近年来发现的一种具有增生性息肉和典型腺瘤结构特征的腺瘤。为了了解基因调控在锯齿状瘤形成途径进展中的作用，我们检测了19个基因启动子区的甲基化谱、DNA倍性和突变体表型状态。在所有的，40散发，经典锯齿状腺瘤进行了病理审查，并根据其组织学分级分为四个病理组。使用p16、hMLH 1、RASSF 1A、APC、HIC-1、DAPK、MGMT、SLC 5A 8、RB 1、H-Cadherin、E-Cadherin、TIMP 3、PTEN、THBS 1、LKB 1、p14、p15、FHIT和VHL的引物进行甲基化特异性PCR。还进行了使用细胞角蛋白和DAPI的双重流式细胞术分析以及使用BAT 26的MSI研究。在16个基因的启动子区域中，2.5-82.5%（平均33.9%）的CpG岛存在甲基化。组织学分级较高的肿瘤，包括癌，与组织学分级较低的肿瘤相比，显示出更广泛的甲基化，并且右侧结肠的锯齿状腺瘤比左侧结肠的锯齿状腺瘤显示出更频繁的甲基化（P
Serrated adenoma is a recently described entity characterized by having combined architectural features of hyperplastic polyps and classical adenoma. To understand the role of gene regulation in the progression of the serrated neoplasia pathway, we examined the methylation profiles of the promoter regions of 19 genes, DNA ploidy, and mutator phenotype status. In all, 40 sporadic, classical serrated adenomas were pathologically reviewed and divided into four pathologic groups according to their histologic grades. Methylation-specific PCR was performed using primers for p16, hMLH1, RASSF1A, APC, HIC-1, DAPK, MGMT, SLC5A8, RB1, H-Cadherin, E-Cadherin, TIMP3, PTEN, THBS1, LKB1, p14, p15, FHIT, and VHL. Dual flow-cytometric analyses using cytokeratin and DAPI and MSI studies using BAT26 were also performed. Methylation was observed in 2.5-82.5% (mean 33.9%) of the CpG islands in the promoter regions of 16 genes. The tumors with higher histologic grades, including carcinomas, showed more extensive methylation compared to those with lower grades, and serrated adenomas in the right colon showed more frequent methylation than those in the left (P