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2000 Fiscal Year Final Research Report Summary

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

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)
Project Period (FY) 1998 – 2000
Keywordsyeast-based genetic diagnosis / stop codon assay / PTEN / NF2 / APC gene / yeast ADE2 gene
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).

  • Research Products

    (12 results)

All Other

All Publications (12 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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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

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Published: 2002-03-26  

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