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Isolation of Putative Tumor Suppressor Genes in Pathogenesis of Ovarian Cancer and Investigation of Micrometastasis in Lymph Nodes of Ovarian Cancer

Research Project

Project/Area Number 10671567
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionJichi Medical School

Principal Investigator

SUZUKI Mitsuaki  Jichi Medical School, Department of Obstetrics and Gynecology, Professor, 医学部, 教授 (50110870)

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
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
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)
Keywordsovarian cancer / tumor suppressor gene / 6q27LOH / AF-6 / replication error / K-ras / p53 / micrometastasis / endometrial cancer / immunohistochemistry
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.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] Suzuki,M.: "Immunohistochemical investigation of thymidylate synthase in cervical cancer"Oncology. 55. 564-568 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Suzuki,M.: "Loss of heterozygosity on chromosome 6q27 and p53 mutations in epithelial ovarian cancer"Med Oncol. 15. 119-123 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ohwada,M.: "DNA replication error in endometrial carcinoma and complex atypical endometrial hyperplasia"Cancer Genet Cytogenet. 114. 130-135 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kashima,K.: "Screening of BRCA1 mutation using immunohistochemical staining with C-terminal and N-terminal antibodies in familial ovarian cancers"Jpn J Cancer. 91. 399-409 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ohwada,M.: "DNA replication errors are frequent in mucinous cystadenocarcinoma of the ovary"Cancer Genet Cytogenet. 117. 61-65 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ohwada,M.: "Mutational analysis of transforming growth factor β receptor type II and DNA mismatch repair genes in sporadic endometrial carcinomas with microsatellite instability"Oncol Rep. 7. 789-792 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Suzuki,M.: "DNA replication error is frequent in ovarian granulosa cell tumors"Cancer Genet Cytogenet. 122. 55-58 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Suzuki,M.: "Mutation of K-ras protooncogene and loss of heterozygosity on 6q27 in serous and mucinous ovarian carcinomas"Cancer Genet Cytogenet. 118. 132-135 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Suzuki,M.: "Micrometastatic p53-positive cells in the lymph nodes of early stage epithelial ovarian cancer : Prognostic significance"Oncology. (in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Suzuki, M., et al.: "Imnunohistochemical investigation of thymidylate synthase in cervical cancer"Oncology. 55. 564-568 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Suzuki, M., et al.: "Loss of heterozygosity on chromosome 6q27 and p53 mutations in epithelial ovarian cancer"Med. Oncol.. 15. 119-123 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ohwada, M., Suzuki, M., et al.: "DNA replication error in endometrial carcinoma and complex atypical endometrial hyperplasia"Cancer Genet Cytogenet. 114. 130-135 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kashima, K., Suzuki, M., et al.: "Screening of BRCA1 mutation using immunohistochemical staining with C-terminal and N-terminal antibodies in familial ovarian cancer"Jpn J Cancer Res. 91. 399-409 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ohwada, M., Suzuki, M., et al.: "DNA replication errors are frequent in mucinous cystadenocarcinoma of the ovary"Cancer Genet Cytogenet. 117. 61-65 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ohwada, M., Suzuki, M., et al.: "Mutational analysis of transforming growth factor βreceptor type II and DNA mismatch repair genes in sporadic endometrial carcinomas with microsatellite instability"Oncol Rep. 7. 789-792 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Suzuki, M., et al.: "DNA replication error is frequent in ovarian granulosa cell tumors"Cancer Genet Cytogenet. 122. 55-58 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Suzuki, M., et al.: "Mutation of K-ras protooncogene and loss of heterozygosity on 6q27 in serous and mucinous ovarian carcinomas"Cancer Genet Cytogenet. 118. 132-135 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Suzuki, M., et al.: "Micrometastatic p53-positive cells in the lymph nodes of early stage epithelial ovarian cancer : Prognostic significance"Oncology. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Suzuki,M.: "DNA replication error is frequent in ovarian granulosa cell tumors"Cancer Genet Cytogenet. 122. 55-58 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Suzuki,M.: "Mutation of K-ras protooncogene and loss of heterozygosity on 6q27 in serous and mucinous ovarian carcinomas"Cancer Genet Cytogenet. 118. 132-135 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Suzuki,M.: "Clinical significance of combined use of macrophage colony-stimulating factor and squamous cell carcinoma antigen as a selective diagnostic marker for squamous cell carcinoma arising in mature cystic ceratoma of the ovary"Gynecol Oncol. 79. 300-304 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ohwada,M: "DNA replication errors are frequent in mucinous cystadenocarcinoma of the ovary"Cancer Genet Cytogenet. 117. 61-65 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ohwada,M: "Mutational analysis of transforming growth factor β receptor type II and DNA mismatch repair genes in sporadic endometrial carcinomas with microsatellite instability"Oncol Rep. 7. 789-792 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kashima,K: "Screenign of BRCA1 mutation using immunohistochemical staining with C-terminal and N-terminl antibodies in familial ovarian cancers"Jpn J Cancer Res. 91. 399-409 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Suzuki, M.: "Enhanced expression of thymidylate synthase may be of prognostic importance in advanced cervical cancer"Oncology. 57. 50-54 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ohwada, M.: "DNA replication error in endometrial carcinoma and complex atypical endometrial hyperplasia"Cancer Genet Cytogenet. 114. 130-135 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Suzuki, M.: "A patient with brain metastasis from ovarian cancer who showed complete remission after multidisciplinary treatment"Gynecol Oncol. 74. 483-486 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Suzuki,M.: "Loss of heterozygosity on chromosome 6q27 and p53 mutations in epithelial ovarian cancer" Med.Oncol.15. 119-123 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Suzuki,M.: "Immunohistochemical investigation of thymidylate synthase in cervical cancer" Oncology. 55. 564-568 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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