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Mutation of the PTEN gene in advanced cervical cancer correlated with tumor progression and poor outcome after radiotherapy

Research Project

Project/Area Number 11670919
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Radiation science
Research InstitutionKANSAI MEDICAL UNIVERSITY

Principal Investigator

HARIMA Yoko  Kansai Med. Univ.. Faculty of Medicine, Associate Professor, 医学部, 助教授 (80140276)

Co-Investigator(Kenkyū-buntansha) IMAMURA Masahiro  Kansai Med. Univ.. Faculty of Medicine, Research associate, 医学部, 助手 (40268339)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1999: ¥1,700,000 (Direct Cost: ¥1,700,000)
KeywordsCervical carcinoma / Radiotherapy / Radioresistant cancer / PTEN gene / Predictive marker / 癌抑制遺伝子 / 染色体ヘテロ接合性消失 / 予後予測
Research Abstract

Improvement of management of advanced cervical cancer after radiotherapy requires a better understanding of its biological behavior. PTEN MMAC TEP (PTEN), a candidate tumor suppressor gene located at chromosome 10q23.3 was recently identified and found to be frequently mutated in several different types of human tumors. In contrast rare mutations of the PTEN gene have been reported in cervical cancer. The aim of this study was to determine whether mutation of PTEN leads to increase genomic alteration in advanced cervical carcinoma and to identify the correlation between mutation of PTEN and patient outcome after radiotherapy. We examined 50 primary advanced cervical carcinomas (37 patients of Stage IIIB.13 patients of Stage IVA) treated with definitive radiotherapy specimens using a PCR-based assay followed by SSCP and direct sequencing. The PTEN gene was mutated in 8 of the 50 (16%) patients (2 of Stage III, and 6 of Stage IV). There was a significant difference in Stage III versus IV between the wild-type PTEN patients and mutant PTEN patients (P=0.002). The tumor size was 6±2.1 cm in the wild-type PTEN tumors versus 8.5±2 cm in the mutant PTEN tumors (P=0.009). In addition, there was a significant difference in survival between the wild-type PTEN patients and mutant PTEN patients (P=0.009). The results of this study suggest that the PTEN gene mutation rate increases with tumor progression, and that the PTEN gene may play a role in both progression of cervical carcinoma and treatment outcome.

Report

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

    (29 results)

All Other

All Publications (29 results)

  • [Publications] Yoko Harima: "Mutation of the PTEN gene in advanced cervical cancer correlated with tumor progression and poor outcome after radiotherapy"International Journal of Oncology. 18. 493-497 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yoko Harima: "Polymorphism of the WAF1 gene is related to susceptibility of cervical cancer in Japanese women"International Journal of Molecular Medicine. 7. 261-264 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yoko Harima: "A randomized clinical trial of radiation therapy versus thermoradiotherapy in stage IIIB cervical carcinoma"International Journal of Hyperthermia. 17. 97-105 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yoko Harima: "Bax and Bcl-2 protein expression following radiation therapy versus radiation plus thermoradiotherapy in Stage IIIb cervical carcinoma"Cancer. 88. 131-137 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yoko Harima: "Loss of heterozygosity on chromosome 6p21.2 as a potential marker for recurrence after radiotherapy of human cervical cancer"Clinical Cancer Research. 6. 1079-1085 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yoko Harima: "Genetic alterations on chromosome 17p associated with response to radiotherapy in bulky cervical cancer"British Journal of Cancer. 81. 108-113 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 播磨洋子: "ハイパーサーミアの臨床 遺伝子異常とハイパーサーミアの効果"松田忠義,菅原努,阿部光幸,田中敬正 編集 医療科学社. 445 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yoko Harima, Satoshi Sawad, Kenji Nagata, Mitsuharu Sougawa, Valentina Ostapenko, Takeo Ohnishi: "Mutation of the PTEN gene in advanced cervical cancer correlated with tumor progression and poor outcome after radiotherapy."International Journal of Oncology. 18. 493-497 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yoko Harima, Satoshi Sawad, Kenji Nagata, Mitsuharu Sougawa, Valentina Ostapenko, Takeo Ohnishi: "Polymorphism of the WAF1 gene is related to susceptibility of cervical cancer in Japanese women."International Journal of Molecular Medicine. 7. 261-264 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yoko Harima, Kenji Nagata, Keizo Harima, Valentina V.Ostapenko, Yoshimasa Tanaka, Satoshi Sawada: "A randomized clinical trial of radiation therapy versus thermoradiotherapy in Stage IIIB cervical carcinoma"International Journal of Hyperthermia. 17. 97-105 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yoko Harima, Kenji Nagata, Keizo Harima, Atsutoshi Oka A, Valentina V.Ostapenko, Nobuaki Shikata, Takeo Ohnishi, Yoshimasa Tanaka: "Bax and Bcl-2 protein expression following radiation therapy versus radiation plus thermoradiotherapy in Stage IIIB cervical carcinoma."Cancer. 88. 131-137 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yoko Harima, Keizo Harima, Satoshi Sawada, Yoshimasa Tanaka, Seizaburo Arita, Takeo Ohnishi: "Loss of heterozygosity on chromosome 6p21.2 as a potential marker for recurrence after radiotherapy of human cervical cancer."Clinical Cancer Research. 6. 1079-1085 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Atsutoshi Oka, Yoko Harima, Keizo Harima, Valentina V.Ostapenko, Yoshimasa Tanaka, Takeo Ohnishi, Satoshi Sawada: "Determination of p53-mediated transactivational ability in radiation-treated cervical cancer."Cancer Detection & Prevention. 24. 275-282 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yoko Harima, Syuya Shirahama, Keizo Harima, Satomi Aoki, Takeo Ohnishi, Yoshimasa Tanaka: "Genetic alterations on chromosome 17p associated with response to radiotherapy in bulky cervical cancer."British Journal of Cancer. 81. 108-113 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yoko Harima: "Mutation of the PTEN gene in advanced cervical cancer correlated with tumor progression and poor outcome after radiotherapy"International Journal of Oncology. 18(In press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yoko Harima: "Polymorphism of the WAFI gene is related to susceptibility of cervical cancer in Japanese women"International Journal of Molecular Medicine. 17(In press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yoko Harima: "Bax and Bel-2 protein expression following radiation therapy versus radiation plus thermoradiotherapy in Stage IIIb cervical carcinoma"Cancer. 88. 131-137 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yoko Harima: "Loss of heterozygosity on chromosome 6p21.2 as a potential marker for recurrence after radiotherapy of human cervical cancer"Clinical Cancer Research. 6. 1079-1085 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Atsutoshi Oka: "Determination of p53-mediated transactivational ability in radiation-treated cervical cancer"Cancer Detection and Prevention. 24. 275-282 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yoko Harima: "Genetic alterations on chromosome 17p associated with response to radiotherapy in bulky cervical cancer"British Journal of Cancer. 81. 108-113 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] 播磨洋子: "ハイパーサーミアの臨床 遺伝子異常とハイパーサーミアの効果"松田忠義,菅原努,阿部光幸,田中敬正 編集医療科学社. 445 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yoko Harima: "Bax and Bcl-2 expression predict response to radiotherapy in human cervical cancer"J Cancer Res Clin Oncol. 124. 503-510 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yoko Harima: "Genetic alterations on chromosome 17p associated with response to radiotherapy in bulky cervical cancer"Br J Cancer. 81(1). 108-113 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yoko Harima: "Bax and Bcl-2 protein expression following radiation therapy versus radiation plus thermoradiotherapy in Stage IIIb cervical carcinoma"Cancer. 88(1). 131-137 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yoko Harima: "Loss of heterozygosity on chromosome 6p21.2 as a potential marker for recurrence after radiotherapy of human cervical cancer"Clin Cancer Res. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Atsutoshi Oka: "Determination of p53-mediated transactivational ability in radiation-treated cervical cancer"Cancer Detect Prev. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Imamura M: "Damage to DNA purified from the radioresitant prokaryote, Deinococcus radiodurans, by acid heating"Int J Mol Med. 3. 391-395 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 播磨洋子: "ハイパーサーミアの臨床 遺伝子異常とハイパーサーミアの効果"松田忠義、菅原 努、阿部光幸、田中敬正、編集 医療科学社. 445 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 播磨洋子: "癌の放射線治療 放射線感受性予測法"田中敬正、平岡眞寛、赤木清、笹井啓資 編集 金芳堂. 234 (1998)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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