2002 Fiscal Year Final Research Report Summary
IDENTIFICATION OF TESTICULAR GERM CELL TUMOR SUSCEPTIBLE GENE ON Xq27 AND INVOLVEMENT OF X INACTIVATION IN TESTICULAR GERM CELL TUMOR TUMORGENESIS
| Project/Area Number |
13671647
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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 |
OKADA Yusaku Professor, Department of Urology, Shiga University of Medical Science, 医学部, 教授 (20127062)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIKI Tatsuhiro Associate Professor, Department of Urology, Shiga University of Medical Science, 医学部, 助教授 (80230704)
SUGIHARA Hiroyuki Associate Professor, Department of Urology, Shiga University of Medical Science, 医学部, 助教授 (30171169)
OKAMOTO Keisei Research Assistanr, Department of Urology, Shiga University of Medical Science, 医学部, 助手 (50303780)
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| Project Period (FY) |
2001 – 2002
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| Keywords | testicular cancer / gain of chromosome / X chromosome / oncogenes / tumor suppressor gene |
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| Research Abstract |
An overabundance of X chromosomes in testicular germ-cell tumors (TGCTs), and the identification of a candidate TGCT susceptibility gene (TGCT1) on Xq27 highlight the potential involvement of X chromosomes in TGCT pathogenesis. The initial part of the present study was designed to shed light on the question whether the multiple X chromosomes in TGCT are active or inacive through a complex mechanism of X chromosomal gain and XIST expression. In the initial part of the present study 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. Furthermore, by showing overexpression of the X-linked oncogenes ARAF1 and ELK1 in TGCT cell lines, we have suggested the potential significance of the supernumerical X chromosomes in TGCT tumorgenesis. The latter half of this study was designed to show the methylation profiles of multiple CpG islands in testicular germ cell tumors in comparison with those in testicular malignant lymphomas. In this part, we have shown that methylation was not observed in E-cadherin, CDKN2B, CDKN2A, BRCA1, RB1, VHL, RASSF1A, RARB and GSTP1 in any TGCT tissues of our series. In contrast, testicular lymphoma tissues demonstrated hypermethylation of E-cadherin, RASSF1A and RARB. These data demonstrate that a distinctive epigenetic phenorype underlies the TGCTs and testicular lymphomas at the CpG sites of E-cadherin, RASSF1A and RARB ; a distinctive epigenetic phenotype was not observed among seminomatous TGCTs and non-seminomatous TGCTs at the CpG sites examined.
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