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Alterations in oncogenes and tumor suppressor genes on human lung cancer as a treament guideline

Research Project

Project/Area Number 04454351
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Thoracic surgery
Research InstitutionKYUSHU UNIVERSITY (1994)
University of Occupational and Environmental Health, Japan (1992-1993)

Principal Investigator

MITSUDOMI Tetsuya  Kyushu University, Faculty of Medicine Research Associate, 医学部, 助手 (70209807)

Co-Investigator(Kenkyū-buntansha) 白日 高歩  産業医科大学, 医学部, 教授 (20038863)
Project Period (FY) 1992 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1994: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1993: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1992: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordslung cancer / prognosis / p53 gene / rb gene / LOH / 3p / 9p / microsatellite polymorphism / 癌遺伝子 / 腫瘍抑制遺伝子 / 治療指針 / 免疫組織化学 / 外科 / 予后因子 / 突然変異 / 予後因子
Research Abstract

The objective of the present study is to investigate various genetic lesions in human lung cancer and to correlate the findings with clinicopathological features including patient prognosis.
First, we examined 120 cases of lung cancer operated on at the Fukuoka University and the University of Occupational and Environmental Health, Japan (UOEH) for p53 mutations. We showed that p53 mutations were a poor prognostic factor especially in advanced cases. However, this cohort was from two institutions and was not fully consecutive. The following analysis was performed using 129 patients out of 140 consecutive patients who were treated at the UOEH.
We examined this cohort for p53 abnormality at a DNA and protein level using immunohistochemistry and SSCP analysis, respectively. In this cohort, p53 mutations were a poor prognostic factor in adenocarcinoma, but there was no significant impact on survival in squamous cell carcinoma.
We then examined loss of heterozygosity at the 3p.5q, 9p locus usi … More ng a microsatellite polymorphism in collaboration with Dr.Adi Gazdar at the University of Texas. LOHs were found in 51,31 and 23%, respectively. Patients with 3p LOH had a poor prognosis in early stage group. However, the other lesions seemed not to be correlated with patient prognosis. Loss of expression of retinoblastoma gene was examined using immunohistochemistry in collaboration with Dr.William Benedict at the Baylor College of Medicine. This abnormality was found in 22% of cases, butthere was no relationship with patient prognosis.
Multivariate analysis for overall survival including above genetic lesions revealed that completeness of the resection was the only determinant for a poor prognosis. However, for a disease free interval in stage I patients, the multivariate analysis indicated that 3p LOH was the only significant predictor for an early disease relapse.
In conclusion, p53 and 3p may be useful markers for clinical oncology of lung cancer. However, there were no genetic prognostic indicator superior to the marker such as a disease stage which are being used routinely. Less

Report

(4 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • 1992 Annual Research Report
  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Mitsudomi,T.: "Detection and sequencing of p53 gene mutation in bronchial biopsy samples in patients with lung cancer [letter]" Chest. 106. 1309-1310 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 光冨徹哉: "肺癌における癌遺伝子腫瘍抑制遺伝子の変化" The Lung perspectives. 2. 135-141 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mitsudomi,T.: "p53 in non-small cell lung cancer[letter]" J.Nat.Cancer Inst.86. 801-803 (1944)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Osaki,T.,,et al.: "Serum concentration and tissue expression of c-erbB2 protein in patients with non-small cell lung cancer." Chest. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mitsudomi T,et al.: "p53 nuclear immunostining and gene mutations in non-small cell lung cnacer and their effect on patient survival." Ann.Oncol.,. (in press.).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kishimoto,Y,et al.: "Frequent loss of short arm of chromosome 9 in resected non-small cell lung cancers from Japanese patients and its association with squamous cell carcinoma." J.Cancer Res.Clin.Oncol.,. (in Press.).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mitsudomi, T., et al.: "Detection and sequencing of p53 gene mutation in bronchial biopsy samples in patients with lung cancer [letter]." Chest. 106. 1309-1310 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mitsudomi, T., et al.: "Alterations of oncogenes and tumor suppressor genes in human lung cancer (review)" The Lung perspectives. 2. 135-141 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mitsudomi, T., et al.: "p53 in non-small cell lung cancer [letter]" J.Nat.Cancer Inst.86. 801-803 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Osaki, T., et al.: "Serum concentration and tissue expression of c-erbB2 protein in patients with non-small cell lung cancer." Chest. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mitsudomi, T., et al.: "p53 nuclear immunostining and gene mutations in non-small cell lung cancer and their effect on patient survival." Ann.Oncol.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kishimoto, Y., et al.: "Frequent loss of short arm of chromosome 9 in resected non-small cell lung cancers from Japanese patients and its association with squamous cell carcinoma." J.Cancer Res.Chin.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mistudomi,T.: "Detection and sequencing of p53 gene mutation in bronchial biopsy samples in patients with lung cancer [Letter]" Chest. 106. 1309-1310 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 光冨徹哉: "肺癌における癌遺伝子腫瘍抑制遺伝子の変化" The Lung perspectives. 2. 135-141 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Mistudomi,T.: "p53 in non-small cell lung cancer[letter]" J.Nat.Cancer Inst.86. 801-803 (1944)

    • Related Report
      1994 Annual Research Report
  • [Publications] Osaki,T.,et al: "Serum concentration and tissue expression of c-erbB2 protein in patients with non-small cell lung cancer." Chest. (in press).

    • Related Report
      1994 Annual Research Report
  • [Publications] Mitsudomi T,et al.: "p53 nuclear immunostining and gene mutations in non-small cell lung cancer and their effect on patient survival." Ann.Oncol.(in press).

    • Related Report
      1994 Annual Research Report
  • [Publications] Kishimoto,Y,et al.: "Frequent loss of short arm of chromosome 9 in resected non-small cell lung cancers from Japanese patients and its association with squamous cell carcinoma." J.Cancer Res.Clin.Oncol.(in press).

    • Related Report
      1994 Annual Research Report
  • [Publications] Mitsudomi,T.: "Mutations of the p53gene as a predictor of poor prognosis in patients with non-small cell luy cancer" Joural of the Notional Cancer Institute. 85. 2018-2023 (1993)

    • Related Report
      1993 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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