| Project/Area Number |
10671567
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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 | Jichi Medical School |
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Principal Investigator |
SUZUKI Mitsuaki Jichi Medical School, Department of Obstetrics and Gynecology, Professor, 医学部, 教授 (50110870)
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| Co-Investigator(Kenkyū-buntansha) |
SAITO Susumu SRL, Inc., Laboratory of Molecular Medicine, Chief researcher, 染色体解析センター, 主任研究員
OHWADA Michitaka Jichi Medical School, Department of Obstetrics and Gynecology, Associate professor, 医学部, 助教授 (40203955)
斎藤 督 (株)エスアールエル遺伝子, 染色解析センター, 主任研究員
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1998: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | ovarian cancer / tumor suppressor gene / 6q27LOH / AF-6 / replication error / K-ras / p53 / micrometastasis / endometrial cancer / immunohistochemistry |
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| Research Abstract |
The following investigations were conducted with tissue specimens obtained from patients with ovarian cancer. 1) To isolate the putative tumor suppressor gene in the region of chromosome 6q27 in patients with ovarian cancer, we performed exon-trapping. 2) Loss of heterozygosity (LOH) was examined by using RFLP markers. 3) K-ras genes were identified by the PCR-dependent preferential homoduplex formation assay. 4) Microsatellite instability (MI) was investigated with paraffin embedded tissues. 5) Immunohistochemistry of p53 were stained by using the mouse monoclonal antibody DO-7. 6) p53 mutations were detected by PCR-SSCP and sequencing.
The following results were obtained : 1) The incidence of LOH in 6q27 was 41% of ovarian cancer patients ; 53% and 23% in cases of serous carcinoma and in those of mucinous carcinoma, respectively, indicating that the incidence of 6q27LOH was significantly higher in cases of serous carcinoma. 2) The commonly deleted region was narrowed to a length 110 kb, and 4 new genes, including AF-6 related to t (6 ; 11) (q27 ; q23), were identified. 3) The incidence of K-ras mutations at codon 12 was 23% ; 5% and 50% in cases of serous carcinoma and in those of mucinous carcinoma, respectively, indicating that the incidence of the K-ras mutations was significantly higher in cases of mucinous carcinoma. 4) The incidence of MI were significantly higher in the mucinous carcinoma (38%). 5) Overexpression of p53 protein in the ovarian cancer (pT1 or 2, No) was observed in 53% of patients. p53 protein-positive cells were detected in the regional lymph nodes (micrometastasis-positive) in 61% of patients with p53 protein overexpression. In patients with micrometastasis, the prognosis was significantly poorer than that in those without micrometastasis.
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