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発がんにおける突然変異と染色体再構成

Research Project

Project/Area Number 63010037
Research Category

Grant-in-Aid for Cancer Research

Allocation TypeSingle-year Grants
Research InstitutionKyoto University

Principal Investigator

佐々木 正夫  京都大学, 放射線生物研究センター, 教授 (20013857)

Co-Investigator(Kenkyū-buntansha) 吉田 廸弘  北海道大学, 理学部, 助教授 (60001765)
神田 尚俊  東京女子医科大学, 講師 (40075429)
福原 資郎  京都大学, 医学部, 助手 (40142301)
阿部 達生  京都府立医科大学, 教授 (60079746)
高井 新一郎  大阪大学, 医学部, 助教授 (80028513)
Project Period (FY) 1988
Project Status Completed (Fiscal Year 1988)
Budget Amount *help
¥17,000,000 (Direct Cost: ¥17,000,000)
Fiscal Year 1988: ¥17,000,000 (Direct Cost: ¥17,000,000)
Keywords発癌 / 突然変異 / 染色体 / 癌遺伝子 / 網膜芽細胞腫 / 神経芽細胞腫 / ウイルムス腫瘍 / リンパ腫
Research Abstract

ヒト癌を中心に、発癌に働く突然変異とその発現の染色体機構について研究を進めた。網膜芽細胞腫(RB)遺伝子の配偶子性突然変異が父親起源であるほか、骨肉腫の研究からRB遺伝子の体細胞突然変異も父由来の遺伝子に偏って起きるという新事実が明らかになった。MEN2A多内分泌腺腫瘍症の遺伝子は日本人でも第10番染色体に位置することが明らかになったが、この場合、発癌に正常対立遺伝子機能消失は必要でないことが示唆された。ヒト染色体1本を癌細胞に移入する実験では癌形質抑制に働く遺伝子が複数個の染色体に存在し、しかもその遺伝子は腫瘍特異的であることが示唆された。神経芽細胞腫は2n、3n、低4n、高4nの4群に分類できるが、2nと低4n腫瘍は他に比べて生存率が低く、染色体構成が予後予測因子となることがわかった。虹彩欠損を伴わないウイルムス腫瘍では必ずしも第11番染色体の異常は多くなく、第1番染色体の異常のほかに異常の認められない症例も存在する。
ろ胞性リンパ腫に見られるbcl-2遺伝子の再構成は33%であり、多発地域である米国の90%と大きく異なる。9/14転座を持つ非ホジキン型リンパ腫で転座の切断点の単離に成功し、リンパ腫の発生に関係する新しい遺伝子が同定された。この遺伝子は第9番染色体の短腕(p13)にマップされ、約10KbのmRNAをコードする。また、発癌に関係する新しい遺伝子である胃癌由来のトランスフォーミング遺伝子HST1が11g13.3へマップされた。この遺伝子は胃癌細胞で他の遺伝子INT2と同調して増幅しており、11g13に癌関連遺伝子のクラスターの存在を示唆する。DNA塩基クアニンのO^6位のアルキル化は突然変異の重要な決定要因の1つであるが、リンパ芽球様細胞でアルキル転移酵素の活性は固定されたものでなく、何らかのON-OFF機構によっているということが示唆された。

Report

(1 results)
  • 1988 Annual Research Report

Research Products

(66 results)

All Other

All Publications

  • [Publications] Sakai,K.: Cancer Genet.Cytogenet.30. 119-126 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Ejima,Y.: Human Genet. 79. 118-123 (1988)

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      1988 Annual Research Report
  • [Publications] Toguchida,J.: Cancer Res.48. 3939-3943 (1988)

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      1988 Annual Research Report
  • [Publications] Sasaki,M.S.: Gann Monogr.Cancer Res.35. 13-28 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Sasaki,M.S.: Jpn.J.Human Genet. 34. 1-16 (1989)

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      1988 Annual Research Report
  • [Publications] Toguchida,J.: Nature. 338. 156-158 (1989)

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      1988 Annual Research Report
  • [Publications] 佐々木正夫: 癌と化学療法. 16. 624-631 (1989)

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      1988 Annual Research Report
  • [Publications] Takai,S.: Gann Monogr.Cancer Res.35. 35-43 (1988)

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      1988 Annual Research Report
  • [Publications] Miki,T.: Genomics. 3. 78-81 (1988)

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      1988 Annual Research Report
  • [Publications] Motoura,K.: Genomics. 2. 180-184 (1988)

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      1988 Annual Research Report
  • [Publications] Okazaki,M.: Mol.Biol.Med.5. 15-22 (1988)

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      1988 Annual Research Report
  • [Publications] Kaneko,Y.: Cancer Res.47. 311-318 (1988)

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      1988 Annual Research Report
  • [Publications] Kaneko,Y.: Lancet. i. 174-175 (1988)

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      1988 Annual Research Report
  • [Publications] Nakajima,F.: Cancer Genet.Cytogenet.30. 163-164 (1988)

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      1988 Annual Research Report
  • [Publications] Ueda,T.: Cancer Genet.Cytogenet.30. 183-185 (1988)

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      1988 Annual Research Report
  • [Publications] Abe,T.: Europ.J.Cancer Clin.Oncol.24. 799-800 (1988)

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      1988 Annual Research Report
  • [Publications] Yokota,S.: Leukemia Res.12. 291-297 (1988)

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      1988 Annual Research Report
  • [Publications] Tominaga,N.: Brit.J.Haematol. 69. 213-218 (1988)

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      1988 Annual Research Report
  • [Publications] Tokumine,Y.: Int.J.Cancer. 42. 99-103 (1988)

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      1988 Annual Research Report
  • [Publications] Okuda,T.: Acta Haematol.80. 110-115 (1988)

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      1988 Annual Research Report
  • [Publications] Horiike,S.: Cancer. 62. 1129-1138 (1988)

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      1988 Annual Research Report
  • [Publications] Maekawa,T.: Cancer Genet.Cytogenet. 34. 261-263 (1988)

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      1988 Annual Research Report
  • [Publications] Nishigaki,H.: Jpn.J.Human Genet.33. 417-421 (1988)

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      1988 Annual Research Report
  • [Publications] Imanishi,H.: J.Chin.Biochem.Nutr.5. 75-79 (1988)

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      1988 Annual Research Report
  • [Publications] Okuda,T.: Leukemia Res.12. 687-692 (1988)

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      1988 Annual Research Report
  • [Publications] Misawa,S.: Leukemia Res.12. 719-729 (1988)

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      1988 Annual Research Report
  • [Publications] Yokota,S.: Jpn.J.Clin.Oncol.18. 321-326 (1988)

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      1988 Annual Research Report
  • [Publications] Yokota,S.: Blut. 58. 27-31 (1989)

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      1988 Annual Research Report
  • [Publications] Inazawa,J.: Cancer Genet.Cytogenet.(1989)

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      1988 Annual Research Report
  • [Publications] Taniwaki,M.: Cancer. (1989)

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      1988 Annual Research Report
  • [Publications] Nishida,K.: Brit.J.Haematol.(1989)

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      1988 Annual Research Report
  • [Publications] Nishida,K.: Cancer Res.(1989)

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      1988 Annual Research Report
  • [Publications] Inazawa,J.: Cytogenet.Cell Genet.(1989)

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      1988 Annual Research Report
  • [Publications] 糸山貴浩: 臨床血液. (1989)

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      1988 Annual Research Report
  • [Publications] Hsu,S.-M.: Blood. 71. 1382-1389 (1988)

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      1988 Annual Research Report
  • [Publications] Abe,M.: Cancer. 61. 483-490 (1988)

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      1988 Annual Research Report
  • [Publications] Matsuda,F.: The EMBO Jounal. 7. 1047-1051 (1988)

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      1988 Annual Research Report
  • [Publications] Nosaka,T.: J.Clin.Invest.81. 1824-1828 (1988)

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      1988 Annual Research Report
  • [Publications] Fukuhara,S.: Blood. 71. 1748-1751 (1988)

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      1988 Annual Research Report
  • [Publications] Kamesaki,H.: Jpn.J.Cancer Res.79. 1193-1200 (1988)

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      1988 Annual Research Report
  • [Publications] Ohno,H.: Cancer Res.48. 4959-4963 (1988)

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      1988 Annual Research Report
  • [Publications] Ohno,H.: Acta Haematol.Japan.51. 1522-1527 (1988)

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      1988 Annual Research Report
  • [Publications] Uchiyama,T.: Blood. 72. 1182-1186 (1988)

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      1988 Annual Research Report
  • [Publications] Amakawa,R.: Blood. 73. 265-272 (1989)

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      1988 Annual Research Report
  • [Publications] Doi,S.: Amer.J.Clin.Pathol.91. 152-158 (1989)

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      1988 Annual Research Report
  • [Publications] Kawakami,T.: Proc.Natl.Acad.Sci.USA. 85. 3870-3874 (1988)

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      1988 Annual Research Report
  • [Publications] Oshimura,M.: Cancer Res.48. 702-708 (1988)

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      1988 Annual Research Report
  • [Publications] Oshimura,M.: Cancer Res.48. 1623-1632 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 押村光雄: 組織培養研究. 6. 12-20 (1988)

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      1988 Annual Research Report
  • [Publications] Koi,M.: Jpn.J.Cancer Res.80. 122-125 (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] Oshimura,M.: Cancer Letter. (1989)

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      1988 Annual Research Report
  • [Publications] Koi,M.: Jpn.J.Cancer Res.(1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] Koi,M.: Mol.Carcinogenesis.

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      1988 Annual Research Report
  • [Publications] Kiyama,Y.: Chromosoma. 96. 372-375 (1988)

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      1988 Annual Research Report
  • [Publications] Tsuchida,Y.: Exptl.Cell Biol.56. 277-284 (1988)

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      1988 Annual Research Report
  • [Publications] Shimatake,H.: Advances in Neuroblastoma Research. 2. 121-131 (1988)

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      1988 Annual Research Report
  • [Publications] Hayashi,Y.: Cancer. (1989)

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      1988 Annual Research Report
  • [Publications] Arita,I.: Mutation Res.208. 167-172 (1988)

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      1988 Annual Research Report
  • [Publications] Yoshida,M.C.: Proc.Natl.Acad.Sci.USA. 85. 4861-4864 (1988)

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      1988 Annual Research Report
  • [Publications] Maru,Y.: Mol.Cell Biol.8. 3700-3776 (1988)

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      1988 Annual Research Report
  • [Publications] Tokino,T.: Cytogenet.Cell Genet.48. 63-64 (1988)

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      1988 Annual Research Report
  • [Publications] Yoshida,M.C.: Gann Monogr.Cancer Res.35. 209-220 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Takahashi,M.: Genomics. 4. 47-52 (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] 児玉靖児: 放射線生物研究. 23. 1-15 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Iijima,S.: Jpn.J.Human Genet.33. 349-353 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 瀧野辰郎: "造血器腫瘍アトラス" 日本医事新報社, 1-70 (1988)

    • Related Report
      1988 Annual Research Report

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Published: 1988-03-31   Modified: 2016-04-21  

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