2006 Fiscal Year Final Research Report Summary
Genome wide analysis of DNA methylation in colorectal cancers in elderly and young patients
| Project/Area Number |
16591348
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Jichi Medical University |
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Principal Investigator |
KONISHI Fumio Jichi Medical University, School of Medicine, Department of Surgery, Professor, 医学部, 教授 (20142242)
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| Co-Investigator(Kenkyū-buntansha) |
MIKI Yoshio Cancer Institute of the Japanese Foundation for Cancer Research, Genetic Research Department, Director, 癌研究所・遺伝子診断研究部, 部長 (10281594)
KAI Toshihiro Jichi Medical University, School of Medicine, Department of Surgery, lecturer, 医学部, 講師 (40260830)
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| Project Period (FY) |
2004 – 2006
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| Keywords | colorectal cancer / DNA methylation / genome wide analysis / MS-RDA / alpha-1-B-adrenergic receptor / G binding protein / gastric cancer / intestinal metaplasia |
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| Research Abstract |
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.
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Research Products
(37 results)
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[Journal Article] Screening for genomic fragments that are methylated specifically in colorectal carcinoma with a methylated MLH1 promoter2005
Author(s)
Koinuma K, Kaneda R, Toyota M, Yamashita Y, Takada S, Choi YL, Wada T, Okada M, Konishi F, Nagai H, Mano H
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Journal Title
Carcinogenesis 26-12
Pages: 2078-2085
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Mutations of BRAF are associated with extensive hMLH1 promoter methylation in sporadic colorectal carcinomas2004
Author(s)
Koinuma K, Shitoh K, Miyakura Y, Furukawa T, Yamashita Y, Ota J, Ohki R, Choi YL, Wada T, Konishi F, Nagai H, Mano H
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Journal Title
Int.J.Cancer 108-2
Pages: 237-242
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Extensive but Hemiallelic Methylation of the hMLH1 Promoter Region in Early-Onset Sporadic Colon Cancers2004
Author(s)
Miyakura Y, Sugano K, Akasu T, Yoshida T, Maekawa M, Saitoh S, Sasaki H, Nomizu T, Konishi F, Fujita S, Moriya Y, Nagai H
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Journal Title
Clinical Gastroenterology and Hepatology 2
Pages: 47-156
Description
「研究成果報告書概要(欧文)」より
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