| Project/Area Number |
11671795
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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 |
Morphological basic dentistry
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| Research Institution | Tohoku University |
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Principal Investigator |
ICHINOHASAMA Ryo Tohoku University, Graduate School of Dentistry, Associate Professor, 大学院・歯学研究科, 助教授 (30184625)
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| Co-Investigator(Kenkyū-buntansha) |
ECHIGO Seishi Tohoku University, Graduate School of Dentistry, Professor, 大学院・歯学研究科, 教授 (70005114)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1999: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | hMSH2 / knock our mouse / TGFβR-II gene / BAX gene / mutation |
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| Research Abstract |
Microsatellite instability has been reported in human lymphomas of follicular center cell origin suggesting that deficient DNA mismatch repair may play a role in the development of these tumors. However, a link between loss of MMR gene expression and abnormalities in tumor suppressor genes targeted by deficient MMR gene function has not been established in follicular lymphoma (FL). We evaluated 22 human t(14;18) chromosomal translocation positive FL cases for abnormalities in hMSH2 and hMLH1 expression and insertion/deletion (ID) mutations within the coding region nucleotide repeats of the BAX and TGF-b receptor type two (TbR-II) genes. Loss of hMSH2 or hMLH1 protein expression within the malignant follicles was identified in 6 of 22 (27%) FL cases by immunohistochemistry (IHC). Sequencing of the entire coding regions of hMSH2 and hMLH1 identified mutations in 2 of 2 FL cases that showed loss of hMSH2 protein expression and in 1 of 4 FL cases that showed loss of hMLH1 protein expressio
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n. There were no mutations in either hMSH2 or hMLH1 in six control FL cases that showed normal expression of these proteins. All six FL cases showing loss of hMSH2 or hMLH1 protein expression were evaluated for ID mutations within the BAX and TRb-II repeats using high fidelity PCR amplification over the repeat areas followed by blunt end cloning and sequencing. ID mutations within the BAX (G)8 and /or TbR-II (A)10 repeats were identified in five of these FL cases whereas all six control FL cases with normal hMSH2 and hMLH1 protein expression lacked ID mutations. Assessment of BAX protein expression by IHC showed absent or markedly diminished expression in 4 of 6 (67%) FL cases that had evidence of deficient MMR gene function, including both FL cases with BAX ID mutations. In contrast, only 3 of 16 (19%) FL cases that lacked evidence of deficient MMR gene function showed absent or diminished expression of BAX protein. These findings implicate deficient MMR gene function in the pathogenesis of human FL and suggest that IHC screening for hMSH2 and hMLH1 protein expression may represent an efficient method to identify FL cases that arise via this pathway. Less
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