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転座関連遺伝子によるがんの診断・病態研究

Research Project

Project/Area Number 08266109
Research Category

Grant-in-Aid for Scientific Research on Priority Areas (A)

Allocation TypeSingle-year Grants
Research InstitutionHiroshima University

Principal Investigator

鎌田 七男  広島大学, 原爆放射能医学研究所, 教授 (00034629)

Co-Investigator(Kenkyū-buntansha) 田中 耕三  広島大学, 原爆放射能医学研究所, 助手 (00304452)
田中 公夫  広島大学, 原爆放射能医学研究所, 助手 (70116622)
宮川 清  広島大学, 原爆放射能医学研究所, 教授 (40200133)
阿部 達生  京都府立医科大学, 医学部, 教授 (60079746)
広沢 信作  東京医科歯科大学, 医学部, 講師 (50143574)
森 茂郎  東京大学, 医科学研究所, 教授 (30010424)
瀬戸 加大  愛知がんセンター, 研究所, 部長 (80154665)
大木 操  国立がんセンター, 研究所, 部長 (00158792)
三谷 絹子  東京大学, 医学部, 助手 (50251244)
Project Period (FY) 1996 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥117,000,000 (Direct Cost: ¥117,000,000)
Fiscal Year 1999: ¥10,000,000 (Direct Cost: ¥10,000,000)
Fiscal Year 1998: ¥37,000,000 (Direct Cost: ¥37,000,000)
Fiscal Year 1997: ¥37,000,000 (Direct Cost: ¥37,000,000)
Fiscal Year 1996: ¥33,000,000 (Direct Cost: ¥33,000,000)
Keywords転座関連遺伝子 / FISH / 慢性骨髄性白血病 / インターフェロン / HLA / WT1 / RAD54 / 造血器腫瘍 / 骨・軟部腫瘍 / FISH法 / AML1遺伝子 / EWS遺伝子 / MLL遺伝子 / BCL6遺伝子 / EVI-1遺伝子
Research Abstract

遺伝子検査をもとに疾病の確定診断、および治療法の開発を行う研究の一端として、慢性骨髄性白血病のインターフェロン(IFN)治療効果をFISH法を用いて判定し、効果の有無とHLA遺伝子多型との相関をみた。治療効果判定を行った116例の解析で、IFN有効例では、A2601,DRB1-0802が、また、無効例ではCw1403のHLAが関与している所見が得られた。IFNの有効性を個体レベル、特にHLA多型性から追求し、関連性の見出されたのは初めてであり、IFN治療対象患者の選択に役立ち、また、ひいては医療費の経済性においても大きく貢献するものと考えられる。
また、転座関連遺伝子の単離を目的として研究し、急性骨髄性白血病(FABM2)でt(12;15)(p13;q25)を持つ症例から、12番染色体上のETV6遺伝子プローブをもとに、12番染色体と転座している15番染色体領域を検出した。解析の結果、ETV6遺伝子のPNTドメインとチロシンキナーゼC(TRKC)遺伝子のPTKドメイン部の結合によることを初めて明らかにした。一方、白血病初期転座に続く悪性化関連遺伝子の1つとして、WT1変異が骨髄性白血病において、また、相同組換え遺伝子RAD54が悪性リンパ腫において関与することを明らかにした。
急性骨髄性白血病の悪性化には、WT1遺伝子変異が一部関与しているため、今後、初診のみならず、治療中、治療後においてもWT1遺伝子変異のスクリーニングを導入する必要がある。

Report

(4 results)
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Eguchi,M.: "Fusion of ETV6 to neurotrophin-3 receptor TRKC in acute myeloid leukemia with t(12;15)(p13;q25)"Blood. 93. 1355-1363 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tanaka,K.: "Detection of 8;21 translocation on interphase cells from acute myelocytic leukemia by fluorescence in situ hybridization and its clinical application"Cancer Genetics & Cytogenetics. 113. 29-35 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Miyagawa,K.: "Mutations of the WT1 gene in childhood nonlymphoid hematological malignancies"Genes Chromosomes & Cancer. 25. 176-183 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hiramoto,T.: "Mutations of a novel human RAD54 homologue, RAD54B, in primary cancer"Oncogene. 18. 3422-3426 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Matsuda,M.: "Mutations in the RAD54 recombination gene in primary cancers"Oncogene. 18. 3427-3430 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Patek,C.E.: "A zinc finger truncation of murine WT1 results in the characteristic urogenital abnormalities of Denys-Drash syndrome"Proc.Natl.Acad.Sci.USA. 96. 2931-2936 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kitabayashi,I.: "The AML1-MTG8 leukemic fusion protein forms a complex with a novel member of the MTG8 (ETO/CDR) family,MTGR1" Molecular & Cell Biology. 18. 846-858 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Eguchi-ishimae,M.: "Fluorescence in situ hybridization analysis of 12 ; 21 translocation in Japanese childhood acute lymphoblastic leukemia" Japanese Journal of Cancer Research. 89. 783-788 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Gamou,T.: "The partner gene of AML1 in t (16 ; 21) myeloid malignancies is a novel member of the MTG8 (ETO) family" Blood. 91. 4028-4037 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ariyama,Y.: "Amplification on double-minute chromosomes and partial-tandem duplication of the MLL gene in leukemic cells of a patient with acute myelogenous leukemia" Genes Chromosomes & Cancer. 23. 267-272 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Narita,M.: "Consistent detection of CALM-AF10 chimeric transcripts in acute leukemia with t (10 ; 11) (p13 ; q14) and identification of novel transcripts" British Journal of Haematology. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Eguchi,M.: "Fusion of ETV6 to neurotrophin-3 receptor TRKC in acute myeioid leukemia with t (12 ; 15) (p13 ; q25)" Blood. 93. 1355-1363 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Suzukawa, K.: "Identification of translocational breakpoints within the intron region before the last coding exon (Exon 12) of the EVI1 gene in two cases of CML-BC with inv (3) (q21q26)" Genemics. 42. 356-360 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ida, K.: "Adenoviral E1 A-associated protein p300 is involved in acute myeloid leukemia with t (11;22)(q23;q13)" Blood. 12. 4699-4704 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ogawa, S.: "Abnormal expression of Evi-1 gene in human leukemias" Human Cell. 9. 323-332 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ueno,H.: "The phosphatidylinositol 3' kinase path way is required for the survival of leukocyte kinase" Oncogene. (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Takita, J.: "Deletion map of chromosome 9 and p16 (CDKN2A) gene alterations in neuroblastoma" Cancer Research. 57. 907-912 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Miyagawa, K.: "Does loss of WT1 function lead to ectopic myogenesis in Wilm's tumors?" Nature Genetics. 18. 15-17 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tanaka, K.: "Frequent jumping translocation of chromosomal segments involving the ABL oncogene alone or in combination with CD3-MLL genes in secondary leukemia" Blood. 89. 596-600 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Morohoshi, F.: "Cloning and mapping of a human RBP56 gene encoding a putative RNA binding protein similar to FUS/TLS and EWS proteins" Genomics. 38. 51-57 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ogawa, S.: "Structurally altered Evi-1 protein generated in the 3q26q21 syndrome" Oncogene. 13. 183-191 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Joh, T.: "Identification of MLL and chimeric MLL gene products involved in 11q23 translocation and possible mechanisms of leukemogenesis by MLL translocation." Int. J. Oncol.13. 1945-1953 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Fujimoto, J.: "Characterication of the transforming activity of p80, a hyperphosphorylated protein in a Ki-1 lymphoma cell line with chromosomal translocation t(2;5)" Proc. Natl. Acad. Sci. USA. 93. 4181-4186 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Inazawa, J.: "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

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Published: 1996-04-01   Modified: 2016-04-21  

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