2006 Fiscal Year Final Research Report Summary
Identification of novel diagnostic tumor marker genes based on genome wide methylation analysis for renal cell carcinoma
| Project/Area Number |
17591683
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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 |
Urology
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| Research Institution | Kochi University |
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Principal Investigator |
KAMADA Masayuki Kochi University, Kochi Medical School Hospital, Lecturer (90304683)
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| Co-Investigator(Kenkyū-buntansha) |
SHUIN Taro Kochi University, Kochi Medical School, Professor (80179019)
OUKOUCHI Hisao Kochi University, Kochi Medical School Hospital, Medical Doctor (60380333)
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| Project Period (FY) |
2005 – 2006
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| Keywords | cancer / gene / methvlation / HOX / RCC / REFERENCES / RCC |
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| Research Abstract |
Epigenetic alterations like DNA methylation and the resulting inactivation of cancer-related genes often contribute to the development of various cancers. To identify the genes that are silenced by aberrant methylation in renal cell carcinoma (RCC), we subjected RCC lines to methylated CpG island/representational difference analysis (MCA/RDA). Subsequent combined bisulfite restriction analysis (COBRA) and bisulfite sequencing analysis of identified CpG islands in primary RCC cases revealed that the human homeo-box gene B13 (HOXB13) gene was methylated in a tumor-specific manner. The methylation frequencies of HOXB13 in primary RCC samples and lines were 30 and 73%, respectively. The methylation status of HOXB13 correlated with the loss of its expression both in RCC lines and primary tumors, and methyltransferase inhibitor (5-aza-dC) treatment induced the recovery of its expression. Exogenous expression of HOXB13 in RCC cells that lacked endogenous HOXB13 expression suppressed cell proliferation and induced apoptosis. Furthermore, HOXB13 methylation correlated positively with tumor grade and microvessel invasion. These results suggest that HOXB13 is a novel tumor suppressor gene in RCC and that its inactivation may play an important role in both RCC tumorigenesis and progression. As HOXB13 is methylated specifically in RCC but not methylated in normal kidney tissues, the methylation of HOXB13 in clinical samples may serve as a valuable diagnostic biomarker for the detection of RCC.
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[Journal Article] Emergency Pancreatoduodenectomy for Pancreatic Metastasis from Renal Cell Carcinoma in a Patient with von Hippel-Lindau Disease : A Case Report2006
Author(s)
Hiromichi Maeda, Takehiro Okabayashi, Michiya Kobayashi, Keijiro Araki, Takuhiro Kosaki, Isao Nishimori, Saburo Onishi, Satoshi Ito, Yasuhiro Ogawa, Heiwa Okuda, Taro Shuin
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Journal Title
Digestive Diseases and Sciences 51(8)
Pages: 1383-1387
Description
「研究成果報告書概要(欧文)」より
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