| Project/Area Number |
09671726
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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 |
Obstetrics and gynecology
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| Research Institution | JAPANESE FOUNDATION OF CANCER RESEARCH |
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Principal Investigator |
HIRAI Yasuo CANCER INSTITUTE, JAPANESE FOUNDATION OF CANCER RESEARCH, RESEARCH FELLOW, 癌研究所・細胞生物部, 研究員 (00260076)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1999: ¥100,000 (Direct Cost: ¥100,000)
Fiscal Year 1998: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1997: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | ENDOMETRIAL CARCINOMA / TGFβRII / BAX / β-catenin / PTEN / MICROSATELLITE INSTABILITY / COMPARATIVE GENOMIC INSTABILITY / MULTISTEP CARCINOGENESIS / TGFβRII / CGH(comparative genomic hybridisation) / TGF β Rll / E2F / 臨床病理学 / 多段階発癌 / エストロゲンリセプター / CGH |
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| Research Abstract |
We analyzed the mutational status of the TGFβRII, BAX, and PTEN/MMAC1 genes as well as microsatellite instability (MI) in 29 consecutive cases of endometrial carcinoma operated on at our Institute. To examine copy number loss at the chromosomal regions bearing these genes, we used comparative genomic hybridization (CGH) analysis. CGH analysis may provides a genome-wide overview about tumor-associated genomic imbalances. Among nine tumors that showed the MI+ phenotype, four (44%) demonstrated a significant mutation with a definite amino acid change in PTEN/MMAC1 gene. CGH analysis demonstrated that all the four tumors (100%) showed chromosomal copy number loss around the locus of this gene, whereas four (57%) of seven tumors with PTEN/MMAC1 mutations showed chromosomal loss or double mutations in MI- carcinomas. The role of TGFβRII and BAX genes is limited as a target gene of MI+ phenotype in endometrial cancer, because several mutations of these genes were detected but a chromosomal loss was demonstrated by CGH in only one tumor in MI+ endometrial cancers with mutation. According to CGH results, chromosomal imbalances were demonstrated at 1q, 9q, 2q, 12q. Frequent abnormal cytoplasmic/ nuclear accumulation of β-catenin was observed in this endometrial series.
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