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疾患遺伝子診断法の開発とその危険因子としての評価

Research Project

Project/Area Number 04670306
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Hygiene
Research InstitutionTokyo Medical and Dental University

Principal Investigator

湯浅 保仁  東京医科歯科大学, 医学部, 教授 (80111558)

Project Period (FY) 1992 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1994: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1993: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1992: ¥1,000,000 (Direct Cost: ¥1,000,000)
Keywords遺伝子診断 / 危険因子 / 遺伝病 / 食道癌 / 大腸癌 / PCR / キャピラリー電気泳動 / 癌抑制遺伝子 / 悪性腫瘍
Research Abstract

1.食道がん
食道がんでがん抑制遺伝子DCCの突然変異と欠失の有無を調べた結果、転移例でDCCの異常が多かった。故にDCC遺伝子は食道がんの転移の危険因子として、遺伝子診断に用いられうることがわかった。
2.大腸がん
遺伝性非腺腫症性大腸がん(HNPCC)でマイクロサテライトDNAを解析したところ、高率にかつ転移がないがんでも異常が起こっていた。この結果は、マイクロサテライトDNAの異常がHNPCCに特徴的な変化であることを示す。
HNPCC家系由来DNAについてhMSH2遺伝子の異常をPCR-SSCP法で検討した。4家系で先天的異常が検出でき、これらの家系では発がんの有無を発症前に遺伝子診断することが可能となった。
3.遺伝子診断自動化のためのキャピラリー電気泳動法の臨床応用
キャピラリー電気泳動法は、直径50μm程度の細いキャピラリー管内でサンプルを電気泳動する方法であり、分離能が高くサンプルを連続的に調べられるので、自動化しやすい特徴があり、我々はこの方法に着目した。遺伝子診断の技術であるPCR-SSCP法・DNAハイブリダイゼーション法による点突然変異の検出系やマイクロサテライト異常の検出系を組み、結果の判定をキャピラリー電気泳動装置を用いて行った。アガロースゲル電気泳動と同等以上の分離能で解析ができ、キャピラリー電気泳動が遺伝子診断に有効であることを確認した。

Report

(3 results)
  • 1994 Annual Research Report
  • 1993 Annual Research Report
  • 1992 Annual Research Report
  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Oto,M.,Yuasa,Y.et al.: "Identification of microsatellite instability in cancer using non-gel sieving capillary electrophoresis." Clinical Chemistry. (in press).

    • Related Report
      1994 Annual Research Report
  • [Publications] Oto,M.,Yuasa,Y.et al.: "DNA hybridization analysis of PCR products by non-gel sieving capillary electrophoresis." PCR Methods & Applications. (in press).

    • Related Report
      1994 Annual Research Report
  • [Publications] Wu,C.,Yuasa,Y.et al.: "DNA alterations in cells from hereditary non-polyposis colorectal cancer patients." Oncogene. 9. 991-994 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Miyake,S.,Yuasa,Y.at al.: "Point mutations and allelic deletion of tumor suppressor gene DCC in human esophageal squamous cell carcinomas and their relation tometastas" Cancer Reserch. 54. 3007-3010 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Arai,T.,Yuasa,Y.et al.: "DNA amplifications and elevated expression of proto-oncogene in addition to altered DNA ploidy in metastatic brain tumors." Clinical and Experimental Metastasis. 12. 267-275 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Homma,M,K.,Yuasa,Y. et al.: "Enhanced phosphoinositide metabolism in colorectal carcinoma cells derived from familial adenomatous polyposis patients." Journal of Cellular Biochemistry. 55. 477-485 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Oto,M.,Yuasa,Y.et al.: "Optimization of non-radioisotopic single strand conformation polymorphism (Non-RI-SSCP) analysis with a conventional minislab gel electrophoresis apparatus." Analytical Biochemistry. 213. 19-22 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kamiyama,T.,Yuasa,Y.et al.: "B-raf oncogene:Activation by rearrangements and assignment to human chromosome 7." Jpn.J.Cancer Res.84. 250-256 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 大藤,湯浅: "銀染色とグラジェントゲルを用いたnonRI PCR-SSCP法" 生化学. 65. 35-38 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Wn,C.,Yuasa,Y.et al.: "DNA alterations in cells from hereditary non-polyposis colorectal cancer patients." Oncogene. 9. 991-994 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Masayuki Ando: "Mutations in c-K-ras 2 gene codon 12 during colorectal tumorigenesis in famitial adenomatous polyposis patients" Gastroenterology. 103. 1725-1731 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Eiko Arai: "A constitutional translocation t(4;22)(9 12;9 12.2)、associated with neurofibromatosis type 2" American Journal of Medical Genetics. 44. 163-167 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Takashi Kamiyama: "B-raf oncogene:Activation by rearrangements and assignment to human chromosome 7" Japanese Journal of Cancer Research. 84. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] 大藤 道衛: "銀染色とグラジェントゲルを用いたnon-RI PCR-SSCP法" 生化学. 65. 35-38 (1993)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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