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Genome wide analysis of DNA methylation in colorectal cancers in elderly and young patients

老年和年轻患者结直肠癌 DNA 甲基化的全基因组分析

基本信息

批准号：
16591348
负责人：
KONISHI Fumio
金额：
$ 2.24万
依托单位：
Jichi Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591348/
关键词：
colorectal cancer DNA methylation genome wide analysis MS-RDA alpha-1-B-adrenergic receptor G binding protein gastric cancer intestinal metaplasia 異常メチル化若年大腸癌細胞増殖抑制能

项目摘要

In order to investigate the genome wide aberrant DNA methylation in colorectal cancer, we used methylation-sensitive representational difference analysis (MS-RDA). For the purpose of excluding methylation caused by ageing, fresh tissues from two colon cancer cases of young age (25 y.o. and 27 y.o.) were used. The genes with methylation in tumor tissue but not in normal mucosa were investigated using MS-RDA method. Thirty-three genes were identified. One of the 33 genes with methylation in tumor tissue but not in normal tissue was alpha-1-B-adrenergic receptor (ADRAJB). The others were genes without functional significance. ADRA1B is one of the G binding proteins. We examined the methylation status of the ADRA1B promoter in 34 paired samples of colorectal cancer and surrounding epithelial tissue, and 34 paired samples of gastric cancer and surrounding epithelial tissue. In colorectal cancers, only four of 34 (11.8%) tumors showed ADRA1B promoter methylation. In contrast, ADRAJB promoter methylation was detected in 24 of 34 (70.6%) gastric cancers and in 14 of 34 (41.2%) surrounding epithelial tissues. The frequency of ADRAJB promoter methylation was higher in gastric epithelial tissues with intestinal metaplasia (41.6%) than in those without intestinal metaplasia (25.0%). Reverse transcription-PCR detected reduced ADRA1B expression in 12 of 18 (66.7%) gastric cancers, and its promoter methylation was detected in 11 of these 12 (91.7%) gastric cancers with reduced ADRA1B expression. Thus, ADRAJB promoter is frequently methylated in gastric cancer. Our results suggest that the ADRAJB gene is an important tumour-related gene frequently involved in the development and progression of gastric cancer.

为了研究结直肠癌全基因组DNA甲基化异常，我们使用甲基化敏感的代表性差异分析（MS-RDA）。为了排除由衰老引起的甲基化，将来自两个年轻年龄（25岁）的结肠癌病例的新鲜组织进行了分析。（27岁）用了采用MS-RDA方法检测肿瘤组织中甲基化基因的表达情况。共鉴定出33个基因。在33个在肿瘤组织中甲基化而在正常组织中没有甲基化的基因中，有一个是α-1-B-肾上腺素能受体（ADRAJB）。其他的是没有功能意义的基因。ADRA 1B是G结合蛋白之一。我们检测了34对结直肠癌和周围上皮组织样本以及34对胃癌和周围上皮组织样本中ADRA 1B启动子的甲基化状态。在结直肠癌中，34例肿瘤中只有4例（11.8%）显示ADRA 1B启动子甲基化。相比之下，ADRAJB启动子甲基化在34例胃癌中的24例（70.6%）和34例癌旁上皮组织中的14例（41.2%）中检测到。有肠上皮化生的胃黏膜组织中ADRAJB基因启动子甲基化率（41.6%）高于无肠上皮化生的胃黏膜组织（25.0%）。逆转录-PCR检测12例（66.7%）胃癌中ADRA 1B表达降低，11例（91.7%）ADRA 1B表达降低的胃癌中检测到启动子甲基化。因此，ADRAJB启动子在胃癌中频繁甲基化。我们的研究结果表明，ADRAJB基因是一个重要的肿瘤相关基因，经常参与胃癌的发生和发展。

项目成果

期刊论文数量（118）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

仮想大腸内視鏡による大腸がんのスクリーニング

通过虚拟结肠镜检查进行结直肠癌筛查

DOI：
发表时间：
2005
期刊：
BIO Clinica 20・1
影响因子：
0
作者：
Jinno H;et al.;Yoshinori Ito;佐々木純一
通讯作者：
佐々木純一

Mutations of BRAF are associated with extensive hMLH1 promoter methylation in sporadic colorectal carcinomas

DOI：
10.1002/ijc.11523
发表时间：
2004-01-10
期刊：
INTERNATIONAL JOURNAL OF CANCER
影响因子：
6.4
作者：
Koinuma, K;Shitoh, K;Mano, H
通讯作者：
Mano, H

Extensive but Hemiallelic Methylation of the hMLH1 Promoter Region in Early-Onset Sporadic Colon Cancers

早发散发性结肠癌中 hMLH1 启动子区域的广泛但半等位基因甲基化

DOI：
发表时间：
2004
期刊：
Clinical Gastroenterology and Hepatology 2
影响因子：
0
作者：
Miyakura Y;Sugano K;Akasu T;Yoshida T;Maekawa M;Saitoh S;Sasaki H;Nomizu T;Konishi F;Fujita S;Moriya Y;Nagai H
通讯作者：
Nagai H

Distribution of lymph node metastasis in T1 sigmoid colon carcinoma: Should we ligate the inferior mesenteric artery?