| Project/Area Number |
03454527
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Hematology
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| Research Institution | Tokyo Women's Medical College |
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Principal Investigator |
MIZOGUCHI Hideaki Tokyo Women's Med. Coll. Fac. Med. Professor, 医学部, 教授 (70049021)
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| Co-Investigator(Kenkyū-buntansha) |
AKAHOSHI Masako Tokyo Women's Med. Coll. Fac. Med. Assistant, 医学部, 助手 (40150974)
HOSHINO Shigeru Tokyo Women's Med. Coll. Fac. Med. Assistant, 医学部, 助手 (30159131)
MOTOJI Toshiko Tokyo Women's Med. Coll. Fac. Med. Lecturer, 医学部, 講師 (00101808)
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| Project Period (FY) |
1991 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 1992: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1991: ¥4,300,000 (Direct Cost: ¥4,300,000)
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| Keywords | MDS / mutations / tumor suppressor gene / 染色体異常 |
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| Research Abstract |
Mutations of the p53 gene have frequently been observed in a wide variety of tumors and are believed to be implicated in the tumorigenesis of these tumors. To determine the relevance of p53 mutations in myelodysplastic syndrome (MDS), we performed polymerase chain reaction-single strand conformation polymorphism analysis on the p53 gene in 28 patients with MDS. We also performed the analysis in 65 patients with various types of haematologic neoplasms. When mobility shifts indicating sequence alterations were detected, subsequent sequencing was performed to identify the mutations. In exons 5 to 8 containing highly conserved regions, mobility shifts were detected in 10 of 93 patients. Sequence analysis showed point mutations in all the ten cases examined. Missense mutations were detected in 5 of the 28 cases of MDS, 1 of 3 cases of adult T-cell leukemia, and 1 of 9 cases of acute lymphoblastic leukemia. A one-base deletion was detected in 1 of 17 cases of myeloma. A nonsense mutation was detected in 1 of 24 cases of chronic myelogenous leukaemia (1 of 7 cases of blast crisis). Most of the mutations were accompanied by loss of the wild type allele. A silent nucleotide substitution was also observed in one case of MDS. Patients harboring these mutations were in advance disease stages. These findings suggest that mutational inactivation of the p53 gene may be involved in the development of MDS.
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