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Development and Application of Yeast Stop Codon Assay for Tumor Suppressor Genes in Brain Tumors

Research Project

Project/Area Number 10470282
Research Category

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

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionHOKKAIDO UNIVERSITY

Principal Investigator

ISHII Nobuaki (2000)  Hokkaido Univ., Grad. School of Med., Instructor, 大学院・医学研究科, 助手 (70312353)

阿部 弘 (1998-1999)  北海道大学, 医学部, 教授 (80000983)

Co-Investigator(Kenkyū-buntansha) IWASAKI Yoshinobu  Hokkaido University, Grad. School of Med., Prof., 大学院・医学研究科, 教授 (00113522)
TADA Mitsuhiro  Hokkaido Univ., Instit. for Genetic Med., Assoc Prof., 遺伝子病制御研究所, 助教授 (10241316)
石井 伸明  北海道大学, 医学部, 助手 (70312353)
澤村 豊  北海道大学, 医学部・附属病院, 講師 (10235476)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥12,700,000 (Direct Cost: ¥12,700,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1998: ¥10,500,000 (Direct Cost: ¥10,500,000)
Keywordsyeast-based genetic diagnosis / stop codon assay / PTEN / NF2 / APC gene / yeast ADE2 gene / yesst-based genetic diagnosis
Research Abstract

In this project, we aimed to identify genes mutated in human brain tumors, by establishing yeast-based assays for chain-terminating mutations, as a new molecular diagnostic tool. We have successfully obtained the following results.
1) We have demonstrated combined mutation or deletion of p53, PTEN, p16, p14ARF genes in human glioblastoma cells (Brain Pathol, 1999).
2) We have demonstrated the role of p53 mutation in malignant progression from low grade astrocytoma to glioblastoma (Oncogene, 1999, Cancer Res, 1999)
3) We have established a yeast assay for p73, and applied it to human brain tumors, together with analyzing the function of the p73 C-terminal part (Cancer Res, 1999 ; Brain Pathol, 2001).
4) We established a PTEN stop codon assay, and demonstrated mutation of PTEN and expression of ψPTEN in glioblastomas (Oncogene, 2000).
5) We established an APC stop codon assay, and applied it to brain tumors, colon cancers, and breast cancers (Am J Pathol, 2000)
6) We have established an NF2 stop codon assay and a "Universal stop codon assay", and applied them to various human tumors (manuscripts in preparation).

Report

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

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Furuuchi K,Tada M et al.: "Somatic Mutations of the APC gene in Primary Breast Cancers."American Journal of Pathology. 156. 1997-2000 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Zhang C-L,Tada M, et al.: "Detection of PTEN nonsense mutation and psiPTEN expression in central nervous system high-grade astrocytic tumors by a yeast-based stop codon assay."Oncogene. 19. 4346-4353 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ozaki T,Tada M, et al.: "Deletion of the COOH-terminal region of p73alpha enhances both its transactivation function and DNA-binding activity but inhibits induction of apoptosis in mammalian cells."Cancer Research. 59. 5902-5907 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Marutani M,Tada M, et al.: "Dominant-negative mutations of the tumor suppressor p53 relating to early onset of glioblastoma multiforme."Cancer Research. 59. 4765-4769 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ishii N,Tada M, et al.: "Cells with TP53 mutations in low grade astrocytic tumors evolve clonally to malignancy and are an unfavorable prognostic factor."Oncogene. 18. 1870-5878 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ishii N,Tada M, et al.: "Frequent co-alterations of TP53, p16/CDKN2A, p14ARF,PTEN/MMAC-1 tumor suppressor genes in human glioma cell lines suggest that p53, Rb and PTEN blong to functionally separate pathways."Brain Pathology. 9. 469-479 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Furuuchi K, Tada M et al.: "Somatic Mutations of the APC gene in Primary Breast Cancers."American Journal of Pathology. 156. 1997-2000 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Zhang C-L, Tada M, et al.: "Detection of PTEN nonsense mutation and psiPTEN expression in central nervous system high-grade astrocytic tumors by a yeast-based stop codon assay."Oncogene. 19. 4346-4353 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ozaki T, Tada M, et al.: "Deletion of the COOH-terminal region of p73alpha enhances both its transactivation function and DNA-binding activity but inhibits induction of apoptosis in mammalian cells."Cancer Research. 59. 5902-5907 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Marutani M, Tada M, et al.: "Dominant-negative mutations of the tumor suppressor p53 relating to early onset of glioblastoma multiforme."Cancer Research. 59. 4765-4769 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ishii N, Tada M, et al.: "Cells with TP53 mutations in low grade astrocytic tumors evolve clonally to malignancy and are an unfavorable prognostic factor."Oncogene. 18. 1870-5878 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ishii N, Tada M, et al.: "Frequent co-alterations of TP53, p16/CDKN2A, p14ARF, PTEN/MMAC-1 tumor suppressor genes in human glioma cell lines suggest that p53, Rb and PTEN blong to functionally separate pathways."Brain Pathology. 9. 469-479 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Furuuchi K, Tada M et al.: "Somatic Mutations of the APC gene in Primary Breast Cancers."American Journal of Pathology. 156. 1997-2000 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Zhang C-L, Tada M, et al.: "Detection of PTEN nonsense mutation and psiPTEN expression in central nervous system high-grade astrocytic tumors by a yeast-based stop codon assay."Oncogene. 19. 4346-4353 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Asaoka K, Tada M et al.: "Efficient adenoviral gene delivery in malignant glioma cells depends on the expression levels of coxsackievirus and adenovirus receptor."Journal of Neurosurgery. 92. 1002-1008 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Furuuchi, K.., Tada, M., et al.: "Somatic Mutations of the APC gene in Primary Breast Cancers"American Journal of Pathology (in press). 未定. (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tada, M., et al.: "Molecular basis of pituitary oncogenesis - a review"Journal of Neuro-Oncology (in peress). 未定. (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nozaki, M., Tada, M., et al.: "Roles of the functional loss of p53 and other genes in astrocytoma tumorigenesis and progression"Neuro-Oncology. 1. 149-162 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ishi, N., Tada M., et al.: "Frequent co-alterations of TP53,p16,p14ARF,PTEN tumor suppressor genes in human glioma cell lines suggest that p53,Rb and PTEN belong to functionally separate pathways"Brain Pathology. 9. 469-479 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nozaki M,Tada M,et al.: "Roles of the functional loss of p53 and other genes in astrocytoma tumorigenesis and progression." Neurooncology. 1(3)(in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Murata J.-I.,Tada M,et al.: "Dysplastic gangliocytoma(Lhermitte-Duclos disease)associated with Cowden disease." Journal of Neuro-Oncology. (in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nakamura H,Tada M,et al: "Identification of a human homolog of the Drosophila neuralized gene within the 10q25.1 malignant astrocytoma deletion region." Oncogene. 16. 1009-1019 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Matsumoto R,Tada M,et al: "Short Alternative Splice Transcripts of Mdm2 oncogene correlate to malignancy in human astrocytic neoplasms." Cancer Research. 58. 608-613 (1998)

    • Related Report
      1998 Annual Research Report

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

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