| Project/Area Number |
15209069
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Surgical dentistry
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
AMAGASA Teruo Tokyo Medical and Dental University, Graduate School, Maxillofacial Surgery, Professor, 大学院・医歯学総合研究科, 教授 (00014332)
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| Co-Investigator(Kenkyū-buntansha) |
INAZAWA Johji Tokyo Medical and Dental University, Medical Research Institute, Department of Molecular Cytogenetics, Professor, 難治疾患研究所, 教授 (30193551)
UZAWA Narikazu Tokyo Medical and Dental University, Graduate School, Maxillofacial Surgery, Research Associate, 大学院・医歯学総合研究科, 助手 (30345285)
IMOTO Issei Tokyo Medical and Dental University, Medical Research Institute, Department of Molecular Cytogenetics, Associate Professor, 難治疾患研究所, 助教授 (30258610)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥43,940,000 (Direct Cost: ¥33,800,000、Indirect Cost: ¥10,140,000)
Fiscal Year 2005: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2004: ¥13,520,000 (Direct Cost: ¥10,400,000、Indirect Cost: ¥3,120,000)
Fiscal Year 2003: ¥25,610,000 (Direct Cost: ¥19,700,000、Indirect Cost: ¥5,910,000)
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| Keywords | Oral cancer / Array-CGH / Genome / Molecular target / DNA methylation |
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| Research Abstract |
1) Banking of primary samples of oral cancer and its premalignant lesions with clinicopathological data
We made collections of cell lines as well as primary samples of oral cancer and its premalignant lesions with clinicopathological data for analyses of cancer genome of this disease.
2) Analysis of genomic copy-number aberration using array-comparative genomic hybridization (array-CGH) and identification of target gene
We analyzed genomic DNA from oral and esophageal cell lines using in-house array-based CGH (MCG Whole Genome Array-4500 and MCG Cancer Array-800). From the regions showing cryptic but remarkable genomic copy-number changes, such as high-level amplification and homozygous deletion, we tried to identify target genes for those aberrations. Together with further analyses using primary tumor samples, we successfully identified many cancer-related genes, including genes correlated with clinicopathological as well as biological significances.
3) Identification of tumor-suppressor genes silenced by DNA methylation using BAC-array-based methylated CpG-island amplification (BAMCA) and Chromatin immunoprecipitation (ChIP) -on-chip method
We combined MCA method to amplify methylated sequences with array-CGH (BAMCA), and screened aberrantly methylated sequences in cancer genome. We also combined ChIP with array-CGH (ChIP-on-chip) for screening of methylated sequences. Using those screening methods with following database search and expression analyses with and without pharmacological modifications, we successfully identified several genes silenced by methylation in esophageal and oral cancers. Among them, candidate tumor-suppressors frequently methylated in oral and esophageal cancers have been successfully identified (unpublished data)
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