| Project/Area Number |
16590601
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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 |
Gastroenterology
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
MATSUMOTO Takayuki Kyushu University, Hospital, Research Associate, 大学病院, 助手 (10278955)
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| Co-Investigator(Kenkyū-buntansha) |
IIDA Mitsuo Kyushu University, Medical Sciences, Professor, 大学院・医学研究院, 教授 (00127961)
NAKAMURA Shotaro Kyushu University, Hospital, Research Associate, 大学病院, 助手 (10243932)
YADA Shinnichiro Kyushu University, Hospital, Research Associate, 大学病院, 助手 (00346800)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2005: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | ulcerative colitis / colorectal cancer / microsatellite instability / p14ARF / p16INK4a / hypermethylation / メチル化 |
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| Research Abstract |
Background : Microsatellite instability (MSI) and CpG island hypermethylation of p14^<ARF> and p16^<INK4a> are presumed to be related to the pathogenesis of neoplasia in ulcerative colitis (UC). We aimed to assess the significance of those genetic and epigenetic alterations for cancer surveillance in patients with UC. Methods : During surveillance colonoscopy in 39 patients with UC, biopsy specimens were obtained from the cecum and the rectum, as well as from the areas suspected of being neoplasia by chromoscopy. Using DNA extracts, methylation status of p14^<ARF> and p16^<INK4a> was assessed by methylation-specific polymerase chain reaction (PCR). MSI status was determined by multiplex PCR for five DNA markers. The methylation status and the MSI status were compared with the result of the index and the subsequent surveillance colonoscopy. Results : MSI was positive in 1 of 5 dysplasias but it was negative in the cecum and in the rectum. The incidence of methylation of p14^<ARF> was 0% in the cecum, 26% in the rectum and 100% in dysplasia, while that of p16^<INK4a> was 10%, 10% and 0%, respectively. Patients positive for methylation of p14^<ARF> in the rectum had a longer duration of UC than those negative for the methylation. Two of 10 patients positive for p14^<ARF> methylation in the rectum and one of 29 patients negative for the methylation had dysplasia. During subsequent surveillance for 36 patients, dysplasia was detected in 2 of 8 patients with p14^<ARF> methylation and in none of 28 patients without the methylation (p=0.044). Conclusions : Hypermethylation of p14^<ARF> is associated with an early stage of dysplasia in UC. The methylation may be a potential biomarker for the identification of UC patients at a high risk of dysplasia.
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