Establishment of algorithm for diagnosis of deficiency of purine metabolizing enzyme MTAP as a molecular target for cancer chemotherapy
| Project/Area Number |
17390163
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Laboratory medicine
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| Research Institution | Mie University |
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Principal Investigator |
NOBORI Tsutomu Mie University, Graduate School of Medicine, Professor (60106995)
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| Co-Investigator(Kenkyū-buntansha) |
SHIRAISHI Taizou Mie University, Graduate School of Medicine, Professor (30162762)
TAKAO Motoshi Mie University, Hosipitat, Associate Professor (30263007)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥14,360,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2007: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2006: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥5,300,000 (Direct Cost: ¥5,300,000)
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| Keywords | MTAP / Gene deletion / Anti-MTAP antibody / Immunostaining / Osteosarcoma / Lung cancer / Selective cancer chemotherapy / Molecular target / DNAメチル化 / 抗MTAPモノクローナル抗体 / エピトープマッピング / 免疫組織染色法 / 細胞周期 |
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| Research Abstract |
Quantitative real-time PCR (qPCR) assay has been used for the diagnosis of MTAP gene deletion. However, the contaminated normal tissues may hamper the accurate evaluation in clinical primary tumor samples. There are some cases which have no immuno-reactive MTAP protein even in absence of MTAP gene deletions. In those cases, qPCR assay cannot diagnose the MTAP deficiency. We analyzed primary tumor samples from non-small cell lung cancer and osteosarcoma with qPCR assay and immunohistochemistry. Of samples analyzed, about 30% had the enzyme deficiency. In cases of MTAP deficiency with the intact MTAP gene, MTAP promoter hypermethylation was detected by the methylation-speciic PCR. In one case of osteosarcoma, MTAP deficiency was not explained by either MTAP gene deletion or promoter hypermethylation.
The results indicated that MTAP deficiency can be diagnosed accurately and easily by the immunohistochemistry with anti-MTAP antibody that we generated rather than by qPCR assay.
Newly developed diagnostic method will be of great help in the development of the selective cancer chemotherapy targeting at MTAP deficiency as a molecular target.
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Report
(4 results)
Research Products
(10 results)
