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FISH法による癌悪性度判定法の開発

Research Project

Project/Area Number 06283223
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

稲澤 譲治  京都府立医科大学, 医学部, 講師 (30193551)

Co-Investigator(Kenkyū-buntansha) 三澤 信一  京都府立医科大学, 医学部, 講師 (40117908)
嘉数 直樹  京都府立医科大学, 医学部, 助手 (20264757)
Project Period (FY) 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥30,000,000 (Direct Cost: ¥30,000,000)
Fiscal Year 1996: ¥10,000,000 (Direct Cost: ¥10,000,000)
Fiscal Year 1995: ¥10,000,000 (Direct Cost: ¥10,000,000)
Fiscal Year 1994: ¥10,000,000 (Direct Cost: ¥10,000,000)
KeywordsFISH / CGH / 染色体異常 / 遺伝子診断 / 遺伝子増幅 / がん / FISH法
Research Abstract

発ガンの過程で複数の遺伝子異常が多段階的に起こり、その蓄積ががんを生物学的にも臨床的にもより悪性の形質獲得へと導く。したがって、既知の癌遺伝子や癌抑制遺伝子の変異に加え、癌抑制遺伝子の存在が推定されている染色体領域の欠失、更に多彩な染色体の過剰変化を検出することで、正確ながん診断が可能となることを意味する。このことからFISH法の技術改良を進め腫瘍に生じたゲノム異常を明らかにし、これらの情報に基づく日常の臨床に応用可能なFISHがん診断法の開発を進めた。頭蓋内腫瘍の一つである髄膜腫(meningioma : MG)の中で、高悪性度群(WHO分類、gradeIII,悪性髄膜腫)において1番染色体短腕(1p)の高頻度欠失を確認し、FISH法による1p欠失判定がMGの悪性度判定に応用可能であることを示した。Comparative genomic hybridization (CGH)法の技術的な標準化をはかり、種々の固形腫瘍、さらに成人性T細胞性白血病(ATL)でのゲノム異常のスクリーニングを行い、新規のゲノム異常を見出し、胃癌において悪性度判定のマーカーに有用である可能性を示した。病理組織学的異型度の確定した乳癌において高頻度の第1番染色体長腕(1q)過剰を見いだし、同領域に乳癌の発生に関わる"優性"のがん関連遺伝子の存在を示し、これが乳癌発症の早期変化であることを明らかにした。
本研究によりFISH癌細胞診断法が、乳癌、膀胱癌、神経膠腫(特に稀突起膠腫)、髄膜腫の癌診断に実地臨床で十分に応用できる遺伝情報に基づいた癌診断技術であることを示された。また、従来の方法では決して容易ではなかった、全染色体を対象にしたゲノム異常のglobal assayが可能となり、新規の病型特異的な染色体異常や遺伝子増幅領域の同定、さらに同領域からのがん関連遺伝子の単離への新しいアプローチに期待がもてる。また、その行程で見出されてくる病型や悪性度に関連したゲノム変化の情報が、新たな癌の染色体・遺伝子異常のマーカーとして利用できる可能性が今回の研究でも示された。

Report

(3 results)
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • 1994 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Inazawa, J. et al.: "PTPN13, a Fas-associated protein tyrosine phosphatase, located on the long arm of chromosome 4 at band q21.3" Genomics. 31. 240-242 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tanaka, T. , Inazawa, J. et al.: "Molecular cloning and mapping of a human cDNA for cytosolic malate dehydrogenesa (MDH1)." Genomics. 32. 128-130 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ichikawa, D. , Inazawa, J. et al.: "Analysis of numerical aberrations in specific chromosomes by fluorescence in situ hybridization (FISH) as a diagnostic tool in breast cancer." Cancer. 77. 2064-2069 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Inazawa, J. , Sasaki, H. et al.: "Precise localization of the human gene encoding cell adhesion kinase β (CAKβ/PYK2) to chromosome 8 at p21.1 by fluorescence in situ hybridization." Human Genetics. 98. 508-510 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nakai, A. , Inazawa, J. et al.: "HSF4, a new member of the human heat shock facyor family which lacks properties of a transcriptional activator." Mol. Coll. Biol.17. 469-481 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kimura, T. , Inazawa, J. et al.: "The brain finger protein gene (ZNF179), a member of the RING finger family, maps within the Smith-Magenis syndrome region in 17p11.2." Am. J. Med. Genetics. (in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] 稲澤譲治: "臨床FISHプロトコール、目で見る染色体・遺伝子診断法" 秀潤社, 192 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ariyama,T.,Inazawa,J.et al.: "High-resolution cytogenetic map of the short arm of chromosome 1 with newly isolated 411 cosmid markers by fluorescence in situ hybrdization;Precise ordering 18 markers on" Genomics. 25. 114-123 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Ariyama,T.,Inazawa,J.et al: "Precise ordering of 26 cosmids markers on 3p21.3->p23 by two-color FISH on prophase chromosomes and stretched DNAs." Cytogent Cell Genet. 70. 129-133 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hashimoto,N.,Inazawa,J.et al.: "Frequent deletion of material from chromosome arm 1p in oligodendroglial tumors revealed by double-target fluorescence in situ hybri-dization and microsatellite analysis." Genes Chromosom Cancer. 14. 295-300 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Morishima,Y.,Inazawa,J.et al.: "Chromosomal loci of 50 human keratinocyte cDNAs assigned by fluorescence in situ hybridization." Genomics. 28. 273-279 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Inagaki,N.,Inazawa,J.et al.: "Reconstitution of IKATP:requirement of both a member of the inward rectifier family of ion channels and the suifonylurea receptor." Science. 260. 1166-1170 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] ICHKawa,D.,Inazawa,J.: "Analysis of numerical aberrations in specific chromosomes by fluorescemce in situ nybridization(FISH)as a diagnostic tool in breast cancer." Cancer. (in press).

    • Related Report
      1995 Annual Research Report
  • [Publications] 稲澤譲治: "分子生物学的アプローチによる癌研究プロトコール(横田淳・山本雅編)" 羊土社, 261 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Inazawa,J.et al.: "High resolution ordering of DNA markers by multi-color fluorescent in situ hybridization of prophase chromosomes." Cytogent Cell Genet.65. 130-135 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Matozaki,T.et al.: "Molecular cloning of a human transmembrane type protein tyrosine phosphatase and its expression in gastrointestinal cancers." J Biol Chem. 269. 2075-2081 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Yoshiura,K.et al.: "Mapping of the 8q23 translocation breakpoint of t(8;13)observed in a patient with multiple exostosies." Genes Chromosome.Cancer.9. 57-61 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Isomura,M.et al.: "Detailed analysis of loss of heterozygosity on chromosome band 17p13 in breast carcinoma on the basis of a high-" Gene Chromosome Cancer. 9. 173-179 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Ariyama,T.et al.: "High-resolution cytogenetic map of the short arm of chromosome 1 with newly isolated 411 cosmid markers by" Genomics. 25. 114-123 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Ariyama,T.: "Precise ordering of 26 cosmids markers on 3p21.3-p23 by multicolor fluorescence in situ hybridization on prophase" Cytogent Cell Genet. (印刷中).

    • Related Report
      1994 Annual Research Report
  • [Publications] 野村慎太郎・稲澤譲治: "脱アイソトープ実験プロトコールDIGハイブリダイゼーション" 秀潤社, 138 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 稲澤譲治: "FISH実験プロトコール" 秀潤社、松原謙一・吉川寛監修, 220 (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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