1997 Fiscal Year Final Research Report Summary
Investigation of the Involvement of Tumor Suppressor Gene and DNA Mismatch Repair Deficiency in Pathogenesis of Ovarian Cancer
| Project/Area Number |
08671919
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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 Associate professor, 医学部, 助教授 (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 Associat professor, 医学部, 講師 (40203955)
KASHIWAGI Hiroshi Jichi Medical School, Department of Surgery Assistant, 医学部, 助手 (30204382)
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| Project Period (FY) |
1996 – 1997
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| Keywords | ovarian cancer / endometrial cancer / tumor suppressor gene / microsatellite instability / DNA mismatch repair gene / 6q27LOH |
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| Research Abstract |
The following investigations were conducted with tissue specimens obtained from patients with ovarian and endometrial cancer. 1) To isolate the putative tumor suppressor gene in the region of chromosome 6q27 in patients with ovarian cancer, loss of heterozygosity (LOH) was examined by using RFLP maekers. 2) Microsatellite instability (MI) was investigated with paraffin embedded tissues. 3) Mutations of four types of DNA mismatch repair genes (MMR) were examined by DNA sequencing and PCR technique.
The following results were obtained : 1) 6q27 LOH was seen in 53% (26/49) of patients with ovarian cancer. The commonly deleted region was narrowed to a length 300kb. Through sequencing analysis of gene fragments obtained by exon trapping and analysis of exons by computer program, 4 new genes, including AF-6 related to t (6 ; 11) (q27 ; q23), were identified. 2) MI was detected in 35% (32/93) of patients with endometrial cancer. MI-positive rates were 14% in stage I,33% in stage II,36% in stage III,and 75% in stage IV,showing significantly higher positive rates in advanced disease (p<0.05). MI was not identified in atypical endometrial hyperplasia. MI was observed in 30% (9/30) of patients with ovarian cancer. 3) Specimens from 14 patients with endometrial cancer were examined for mutations of DNA MMR.No mutation was detected in the regions of MLH1, PMS1 and PMS2 genes. However, mutations of the MSH2 gene at intron splice acceptor sites were idendified in 36% (5/14) of the patients. According to these results, it appears that isolation of the putative tumor suppressor gene in the region of chromosome 6q27 may be achieved in the near future. Results also clarified that DNA mismatch repair deficiency contributes to the pathogenesis of endometrial and ovarian cancer was shown.
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