• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

がん関連遺伝子変異の検出および機能評価法の開発

Research Project

Project/Area Number 12217010
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionTohoku University

Principal Investigator

石岡 千加史  東北大学, 加齢医学研究所, 教授 (60241577)

Co-Investigator(Kenkyū-buntansha) 柴田 浩行  東北大学, 病院・講師 (50260071)
加藤 俊介  東北大学, 病院・助手 (40312657)
千葉 奈津子  東北大学, 加齢医学研究所, 助手 (50361192)
酒寄 真人  東北大学, 病院・助手 (20344666)
Project Period (FY) 2000 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥58,000,000 (Direct Cost: ¥58,000,000)
Fiscal Year 2004: ¥11,100,000 (Direct Cost: ¥11,100,000)
Fiscal Year 2003: ¥11,100,000 (Direct Cost: ¥11,100,000)
Fiscal Year 2002: ¥11,000,000 (Direct Cost: ¥11,000,000)
Fiscal Year 2001: ¥12,800,000 (Direct Cost: ¥12,800,000)
Fiscal Year 2000: ¥12,000,000 (Direct Cost: ¥12,000,000)
Keywords遺伝子変異 / 機能解析 / ミスセンス変異 / p53 / BRCA1 / MYH / MLH1 / missense mutation / PTEN / 機能診断 / BRCA2
Research Abstract

がん抑制遺伝子やDNA修復遺伝子などのがん関連遺伝子の変異を検出し、その変異が遺伝子産物の機能へ及ぼす影響を評価するためのアッセイ系開発とそれを応用することを目的とし平成16年度に下記の成果を得た。1.家族性乳癌遺伝子BRCA1遺伝子産物の機能解析を行いN末近傍のRINGドメインのBARD1結合、ユビキチン化能、細胞増殖抑制能について明らかにし、その部位のミスセンス変異がBRCA1機能に及ぼす影響を解析した。この中でH41RはBIRD1との結合とユビキチン化能障害があり病的変異であった。2.網羅的p53ミスセンス変異ライブラリー(2314種類)を作成し、その中から野生型p53よりもアポトーシス誘導能が強い変異p53(super p53)を多数同定した。3.遺伝性非ポリポーシス大腸癌で報告されているミスマッチ修復遺伝子MLH1のアミノ酸置換型100SNPsについて出芽酵母発現系とヒト細胞発現系で機能解析し、病的変異型、機能野生型に分類した。4.塩基除去修復遺伝子の一つである多発性大腸腺腫の原因遺伝子MYHについて、APC遺伝子変異陰性の家族性大腸腺腫症例について変異解析を行い、1症例に病的変異を認めた。さらに大腸菌のmutY遺伝子変異株にヒトMYH発現を発現し、その機能相補性を利用した変異機能診断法を作成した。
なおヒト遺伝子解析研究は東北大学医学系研究科倫理委員会の承認を得た研究計画に従って実施した。

Report

(4 results)
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (14 results)

All 2005 2004 Other

All Journal Article (5 results) Publications (9 results)

  • [Journal Article] Reassessment of the TP53 mutation database in human disease by data mining with a library of TP53 missense mutations.2005

    • Author(s)
      Soussi, T.ほか
    • Journal Title

      Human Mutation 25

      Pages: 6-17

    • Related Report
      2004 Annual Research Report
  • [Journal Article] CIdentification and evaluation of 55 genetic variations in the BRCA1 and the BRCA2 genes of patients from 50 Japanese breast cancer families.2004

    • Author(s)
      Kawahara, M.ほか
    • Journal Title

      Journal of Human Genetics 49

      Pages: 391-395

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Expression of an amino-terminal BRCA1 deletion mutant causes a dominant growth inhibition in MCF10A cells.2004

    • Author(s)
      You, F.ほか
    • Journal Title

      Oncogene 23

      Pages: 5792-5798

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Collaboration of Breast Cancer Clinic and Genetic Counseling Division for BRCA1 and BRCA2 Mutation Family in Japan.2004

    • Author(s)
      Takeda, M.ほか
    • Journal Title

      Breast Cancer 11

      Pages: 30-32

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Kanamaru, R. and Yoshimoto, T. PTEN gene mutation and high MIB-1 labeling index may contribute to dissemination in patients with glioblastoma.2004

    • Author(s)
      Kato, H.ほか
    • Journal Title

      Journal of Clinical Neuroscience 11

      Pages: 37-41

    • Related Report
      2004 Annual Research Report
  • [Publications] Kato S, et al.: "Understanding the function-structure and function-mutation relationships of p53 tumor suppressor protein by high-resolution missense mutation analysis."Proc.Natl.Acad.Sci., U S A. 100. 8424-8429 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shiraishi K, et al.: "Isolation of temperature-sensitive p53 mutations from a comprehensive missense mutation library."J.Biol.Chem.. 279. 348-355 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kato H, et al.: "PTEN gene mutation and high MIB-1 labeling index may contribute to dissemination in patients with glioblastoma."J.Clin.Neurosci.. 11. 37-41 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Takeda M, et al.: "Division for BRCA1 and BRCA2 mutation family in Japan."Breast Cancer. 11. 30-32 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tsuchida R, et al.: "Detection of ATM gene mutation in human glioma cell line M059J by a rapid frameshift/stop codon assay in yeast"Radiation Research. 158. 195-201 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Otsuka K, et al.: "Analysis of the human APC mutation apectrum in a Saccharomyces cerevisiae strain with a mismatch repair defect"International Journal of Cancer. 103. 624-630 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sakayori M, et al.: "Evaluation of the diagnostic accuracy of the stop codon (SC) assay for identifying protein-truncating mutations in the BRCA1 and BRCA2 genes in familial breast cancer"Journal of Human Genetics. 48. 130-137 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shuan-Yin Han et.al: "Functional evaluation of PTEN missense mutations using in Vitro phosphoinositide phasphatase assay"Cancer Research. 60. 3147-3151 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hideaki kato, et.al.: "Functional Evaluation of p53 and PTEN gene mutations in gliomas"Clinical Cancer Research. 6. 3937-3943 (2000)

    • Related Report
      2000 Annual Research Report

URL: 

Published: 2000-04-01   Modified: 2018-03-28  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi