Analysis of Mismatch repair gene methylation for Gynecologic cancer screening
| Project/Area Number |
16591649
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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 |
Obstetrics and gynecology
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| Research Institution | Department of Clinical Research, National Hospital Organization Kanazawa Medical Center (2005-2006)
Kanazawa University (2004) |
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Principal Investigator |
KANAYA Taro Department of Clinical Research, National Hospital Organization Kanazawa Medical Center, Department of Clinical Research, Research Associate (30303308)
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| Co-Investigator(Kenkyū-buntansha) |
京 哲 金沢大学, 医学系研究科, 講師 (50272969)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Gynecologic cancer / Cancer screening / DNA methylation / Mismatch repair gene / Gene mutation / Endometrial cancer / DNA hypermethylation / Cancer screening |
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| Research Abstract |
We already reported the methylation of MLH1 promoter and the decrease of its protein expression in endometrial cancer, and the mutations of downstream genes with microsatellite instabilities. With this funds, we provided more details as shown.
1. Analysis of MLH1 promoter methylation in endometrial hyperplasia
Because of a very small amount for clinical sample of the endometrium hyperplasia, as a cancer precursor, it was difficult to perform methylation analysis. We developed the method of methylation analysis of the MLH1 promoter from the very small amount of endometrial sample, using PCR after restriction enzyme processing and Bisulfite modification. As a result, 11 of 27 endometrial hyperplasia examples (41%) were methylated, and the methylation frequency was approximately equal with endometrial cancers.
2. Relation with the PTEN mutation
PTEN is a cancer suppressor gene which has mutations in the early stage of endometrial cancers. As a result of PTEN mutation analysis, 38% of the endometrial cancers and 19% of the endometrial hyperplasias have PTEN mutations. We also found complex hyperplasias have more frequent PTEN mutations than simple hyperplasias. We recognize the methylation of MLH1 promoter is upstream of histological changes, and the PTEN mutation is a next step.
3. The methylation and mutation analysis with cytological specimen
In this study, the purpose is gynecologic cancer screening with the combination of cyto-histology and genetic analysis. With our preliminary experiments, cytological specimen has enough samples for methylation and mutation analysis. In future, we have to distinguish the high risk patients for gynecologic carcinogenesis with methylation and mutation analysis of cytological specimens for clinical application.
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Report
(3 results)
Research Products
(11 results)
