Rare CpG island methylator phenotype in ulcerative colitis-associated neoplasias
Rare CpG island methylator phenotype in ulcerative colitis-associated neoplasias
复制标题
DOI：
10.1053/j.gastro.2007.01.035
复制
发表时间：
2007-04-01
期刊：
影响因子：
29.4
通讯作者：
Issa, Jean-Pierre J.
中科院分区：
文献类型：
--
作者：
Konishi, Kazuo;Shen, Lanlan;Issa, Jean-Pierre J.
背景和目的：我们之前报道，在溃疡性结肠炎（UC）患者的发育不良和非发育不良粘膜中发现了高度与年龄相关的甲基化。这是否会转化为 UC 相关癌症 (UC-Cs) 中的高甲基化尚不清楚。方法：我们使用定量亚硫酸氢盐焦磷酸测序评估了 48 例 UC-C、21 例 UC 相关发育不良和 69 例散发性结直肠癌 (S-CRC) 中 11 个基因（MINT1、2、31、hMLH1、p16、p14、MGMT、HPP1、SFRP1、ER α 和 LINE-1）的甲基化状态。 分析。结果：除 MGMT 外，UC-C 中所有基因的甲基化水平均低于 S-CRC。基于 Z 得分平均值的甲基化指数，对于 C 型（癌症特异性基因：MINT1、MINT2、MINT31、hMLH1、p16 和 p14），UC-C 中为 -.97，S-CRC 中为 0.92 (P = .009)。 A 型（年龄相关基因：HPP1、SFRP1 和 ER α）在 UC-C 中为 -1.97，在 S-CRC 中为 1.24（P < .001）。我们观察到 UC-C 和 S-CRC 之间 CpG 岛甲基化表型的发生率存在显着差异（48 例中有 8 例 [17%]，69 例中有 26 例 [38%]；P = 0.022）。 UC 相关不典型增生的 A 型基因甲基化显着高于 UC-C（Z 得分：分别为 0.07 和 -1.97；P < .001）。相比之下，使用 LINE-1 检测测量的整体 DNA 甲基化在 UC-C 中显着高于 S-CRC（58.2% vs 51.0%，P
Background & Aims: We previously reported that a high degree of age-related methylation was found in both the dysplastic and nondysplastic mucosa of patients with ulcerative colitis (UC). Whether this translates into hypermethylation in UC-associated cancers (UC-Cs) is not known. Methods: We evaluated the methylation status of 11 genes (MINT1, 2, 31, hMLH1, p16, p14, MGMT, HPP1, SFRP1, ER alpha, and LINE-1) in 48 UC-Cs, 21 UC-associated dysplasias, and 69 sporadic colorectal cancers (S-CRCs) using a quantitative bisulfite pyrosequencing analysis. Results: Methylation levels in UC-Cs were lower than S-CRCs for all the genes except MGMT. A methylation index based on the average of Z-scores, for type C (cancer-specific genes: MINT1, MINT2, MINT31, hMLH1, p16, and p14) was -.97 in UC-Cs and .92 in S-CRCs (P = .009). That of type A (age-related genes: HPP1, SFRP1, and ER alpha) was -1.97 in UC-Cs and 1.24 in S-CRCs (P < .001). We observed a significant difference in the incidence of CpG island methylator phenotype between UC-Cs and S-CRCs (8 of 48 [17%] and 26 of 69 [38%]; P =.022). UC-associated dysplasias had significantly higher methylation of type A gene than UC-Cs (Z-score: .07 and -1.97, respectively; P < .001). By contrast, global DNA methylation measured using a LINE-1 assay was significantly higher in UC-Cs than in S-CRCs (58.2% vs 51.0%, P