| Project/Area Number |
15591682
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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 |
Urology
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| Research Institution | Department of Urology, Faculty of Medicine, Shiga University of Medical Science |
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Principal Investigator |
NARITA Mitsuhiro (2004) Shiga University of Medical Science, Department of Urology, Research Assistant, 医学部, 助手 (00263046)
川上 享弘 (2003) 滋賀医科大学, 医学部, 助手 (90346023)
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| Co-Investigator(Kenkyū-buntansha) |
OKAMOTO Keisei Shiga University of Medical Science, Department of Urology, Research Assistant, 医学部, 助手 (50303780)
OKADA Yusaku Shiga University of Medical Science, Department of Urology, Professor, 医学部, 教授 (20127062)
SAKANO Yuji Shiga University of Medical Science, Department of Urology, Research Assistant, 医学部, 助手 (00346016)
杉原 洋行 滋賀医科大学, 医学部, 助教授 (30171169)
成田 充弘 滋賀医科大学, 医学部, 助手 (00263046)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | testicular cancer / methylation / X chromosome / XIST / 癌遺伝子 / 癌感受性遺伝子 / エピジェネテイックス / 腫瘍マーカー |
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| Research Abstract |
In this project we found testicular germ-cell tumors(TGCTs) carry unique epigenetic profiles : The DNAs of TGCTs are relatively unmethylated in comparison with those of other somatic tissue derived cancer. Furthermore, we developed a novel DNA tumor marker for testicular germ cell tumors(TGCTs) that is based on the unmethylated DNA profile of a neoplasm.
We have shown that XIST expression in TGCTs is not associated with the methylation of X-linked genes and is therefore mechanistically distinct from the XIST expression in female inactive X chromosomes. Thus, supernumerical X chromosomes in TGCTs were predominantly hypomethylated and active regardless of XIST expression (J.Urol 2003 ).
We have reported that aberrant methylation at the promoter of tumor related genes are common in testicular lymphomas, but not in TGCTs (GCC 2003).
These data suggest that DNA of TGCTs may be ubiquitously regulated as unmethylated.
Thus, it appears difficult to create a methylation-based DNA marker for TGCTs. Alternatively, we hypothesized that unmethylated DNA regions specific for TGCTs, if they exist, could be used as potential DNA markers. Among various genes, we have focused on the XIST gene, which is solely expressed in germ cells among male organs. Unmethylated XIST DNA fragments only exist in female PBLs, but not in male PBLs. We have detected unmethylated XIST DNA fragments in TGCT tissues and matching plasma samples from the patients with TGCTs (Lancet). We also clarified methylation profiles of TGCTs in several cancer testis antigen(CTA) genes (GCC 2005). Mechanisms for maintaining DNA free from methylation in TGCTs are under investigation in comparison with those in primordeal germ cells.
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