| Project/Area Number |
10470336
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | AKITA UNIVERSITY |
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Principal Investigator |
HABUCHI Tomonori School of Medicine, Akita University, Associate Professor, 医学部, 助教授 (00293861)
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| Co-Investigator(Kenkyū-buntansha) |
SATO Kazunori School of Medicine, Akita University, Associate Professor, 医学部, 講師 (90270842)
AKAO Toshiya School of Medicine, Akita University, Lecturer, 医学部, 助手 (40301064)
KATO Tetsuro School of Medicine, Akita University, Professor, 医学部, 教授 (40004642)
KAKEHI Yoshiyuki Graduate School of Medicine, Kyoto University, Associate Professor, 医学研究科, 助教授 (20214273)
FUJITA Jun Graduate School of Medicine, Kyoto University, Professor, 医学研究科, 教授 (50173430)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥8,200,000 (Direct Cost: ¥8,200,000)
Fiscal Year 1999: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1998: ¥4,700,000 (Direct Cost: ¥4,700,000)
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| Keywords | bladder cancer / urothelial cancer / molecular genetics / tumor suppressor gene / chromosome 9 / loss of heterozygosity / multiplicity / microsatellite marker / 染色体9 |
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| Research Abstract |
One of the most important features of urothelial cancers is metachronous and/or synchronous multifocal occurrence with high frequency. If it is found that such multifocal recurrent tumors are derived from a common transformed cell, the chronological tracing of genetic alterations in such multifocal tumors may reveal the precise timing and role of genetic alterations in urothelial carcinogenesis. In this study, we tested the presence of microsatellite alterations in synchronous and/or metachronous multifocal urothelial cancers to examine the chronological genetic alterations for the presence of hierarchy of genetic alterations in urothelial cancer development. Genetic alterations at 20 microsatellite loci on 8 chromosomal arms (2q, 4p, 4q, 8p, 9p, 9q, 11p, and 17p) were tested. Judging from the patterns of allelic deletion and microsatellite shifts, tumors in 80% of patients with multifocal tumors were considered to be derived from a single progenitor cell. In multifocal tumors of an identical clonal origin, discordant microsatellite alterations were observed with significantly lower frequencies on chromosome 9 compare with those on the other chromosomes tested. The data strengthens the previous view that heterotopic spread of transformed progenitor cell and genetic divergence occur after chromosome 9 alterations in most of urothelial cancers. Furthermore, one of the putative tumor suppressor loci on 9q was mapped at 9q32-33 and a gene designated as DBCCR1 was identified. Although it is unclear if DBCCR1 is a real tumor suppressor gene, the exon one is very rich in CpG site and conforms to the criteria of CpG island. Furthermore, its mRNA expression was shown to be suppressed by hypermethylation of the 5'-region and the hypermethylation of DBCCR15'-region was frequently found in TCCs in vivo and in vitro.
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