| Project/Area Number |
14570962
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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 |
Hematology
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| Research Institution | The UNIVERSITY OF TOKYO |
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Principal Investigator |
OGAWA Seishi The University of Tokyo, Faculty of Medicine, Visiting Associate Professor, 医学部附属病院・客員助教授(常勤形態) (60292900)
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| Co-Investigator(Kenkyū-buntansha) |
HHANGAISHI Akira The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (20344450)
KUROKAWA Mineo The University of Tokyo, Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (80312320)
CHIBA Shieru The University of Tokyo, Faculty of Medicine, Associate Professor, 医学部附属病院, 助教授 (60212049)
SUZUKI Takahiro The University of Tokyo, Faculty of Medicine, Visiting Research Associate, 医学部附属病院, 客員助手(常勤形態) (40345210)
KANDA Yoshinobu The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (30334379)
青木 克己 東京大学, 医学部附属病院, 助手 (40291322)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | t(1;7)(q10:910) / del(7q) / methylation analysis / myelodysplastic syndrome / alphoid sequences / CpG islands / Methylation pattern / MDS / CpGアイランド / der(1;7)(q10;p10) / 欠失解析 |
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| Research Abstract |
The unbalanced translocation t(1;7)(q10;p10) and the del(7q) are recurrent chromosomal aberrations found in myelodysplastic syndrome (MDS) and predicts a very poor prognosis. Thus, o improve (heir treatment outcome, it is of particular importance to disclose the molecular pathogenesis of these critical abnormalities, which is our research goal. In (his study we performed genetic analyses of these translocation and deletion, in an attempt to identify the critical gene(s) involved in these aberrations. First, using quantitative FISH analysis using two centromere alphoid probe, DIZ7 and D7ZI from the centromere 1q chromosome I and 7, respectively, we revealed that these two alphoids are directly involved in t(1;7) translocation. Combined with other results, it is postulated that this translocation is generated as a result of misconnect between these. highly homologous alphoids during a recombinational repair process. It is also suggested that Trisomy 1q and monosomy 7q, rather than breakpoint genes are responsible to the pathogenesis. For the targets of del(7q), we performed an comprehensive methylation analysis of CpG islands on 7q, in which a total of 130 CpG islands (60% of all CpG islands on 7q) successfully amplified by bisulfite-PCR were examined for their aberrant methylation using direct sequencing for a number of hematopoietic tumor samples including MDS. Two genes were identified which exist down stream of highly and frequently methlated CpG islands and whose expression was down regulated in a methylation-dependent manner. These are though to be candidates of tumor suppressor genes that is relevant to pathogenesis of MDS with loss of 7q materials and a mutation analysis involving a large number of MDS samples is in progress.
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