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がんの遺伝子診断

Research Project

Project/Area Number 06282116
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Research InstitutionMie University

Principal Investigator

珠玖 洋  三重大学, 医学部, 教授 (80154194)

Co-Investigator(Kenkyū-buntansha) 安井 弥  広島大学, 医学部, 助教授 (40191118)
高橋 隆  愛知県がんセンター研究所, 超微形態学部, 部長 (50231395)
森下 和廣 (森下 和宏 / 森下 和広)  国立がんセンター研究所, 生物学部, 主任研究員 (80260321)
時野 隆至 (時野 隆臣)  東京大学医科学研究所, 分子病態研究施設, 助教授 (40202197)
金子 安比古  埼玉県立がんセンター, 化学療法部, 部長
谷口 直之  大阪大学, 医学部, 教授 (90002188)
Project Period (FY) 1994 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥100,500,000 (Direct Cost: ¥100,500,000)
Fiscal Year 1996: ¥30,000,000 (Direct Cost: ¥30,000,000)
Fiscal Year 1995: ¥35,000,000 (Direct Cost: ¥35,000,000)
Fiscal Year 1994: ¥35,500,000 (Direct Cost: ¥35,500,000)
Keywords癌の遺伝子診断 / 消化器癌 / 肺癌 / 神経芽腫 / 白血病 / 遺伝子診断 / 癌 / 癌遺伝子 / 癌抑制遺伝子
Research Abstract

1.胃癌組織40例において、CDC25Aは45%、CDC25Bは70%(28症例)において発現増強が認められ、CDC25Cは全てで低発現だった。CDC25Bは低分化腺癌症例、ステージの進んだ症例に発現増強が認められた。又、分子病理診断の一つとしてCAr ep eatを2ローカス、polyAを2ローカス検討し、約5%の症例でreplication errorを同定した。分子病理診断は9000例にいたった。
2.208症例の非小細胞癌症例でcyclinD1およびRb遺伝子の検討を行ったところ、cyclinD1遺伝子発現の消失がみられた腺癌症例は、有意に短い術後生存期間を示した。多変量解析でもcyclinD1はp53、病期と共に独立した有意な予後因子だった。
3.神経芽腫106例を対象として、1p36のD1Z1と1q12のD1Z1プローブを用いてFISH法で検討した。D1Z1の数(n数)、およびD1Z1数に比してのD1Z2数(D1Z1>D1Z2;b;D1Z1=D1Z2;a)更に、RFLPマーカーによる1pのLCH、及びN-myc増幅を合わせて検討した。その結果、2nb、4nb腫瘍は予後不良、3n、5n腫瘍は予後良好、2na、4na腫瘍はその中間であった。
4.急性骨髄性白血病における第三染色体の異常をEVI1遺伝子を中心として解析した。t(3;7)転座を有する症例、t(1;3)転座を有する症例の切断点および遺伝子を同定した。又40症例の白血病においてガングリオシドGM3からのGD3の合成酵素、α2,8シアル酸糖転移酵素の発現を検討したところ、T-ALLで中等度の、ATLで高い遺伝子発現が認められた。
5.p53の下流標的遺伝子の検索を進め、8種類の正常型p53により発現制御される遺伝子を同定した。そのひとつはGPl anchor ed mol eculeに属する新しい遺伝子であり、その発現は食道癌細胞株の抗癌剤感受性と強い相関性を示した。
6.AFPやγ-GTPの糖鎖に癌性変化を起こすα1,6 fucosyltr ansfer aseの精製を行いそのcDNAを単離した。

Report

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

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Yamaguchi A,et al.: "Expression of a CD44 variant containing exons 8 and 10 is a useful independent factor for the prediction of prognosis in colorectal cancer patients" J.Clin.Oncol.14. 1122-1127 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Takeda O,et al: "An in creased NM23H1 copy number may be a poor prognostic factor independent of 20H on 1p in neuroblastomas." Brit.J.Cancer,. 74. 1620-1626 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kimura Y,et al: "Genomic structure and chromosomal localization of GML(GPl-anchored molucule-like protein),a gene induced by p53." Genomics. (in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Taki T,et al: "Fusion of the MLL gene with two different genes,AF-6 and AF-5a,by a complex translocation involving chromosomes 5,6,8,and 11 in infant leukemia." Oncogene. 13. 2121-2130 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nishio M,et al: "Prognostic significance of abnormal p53 accumulation in primary,resected non-small lung cancers." J.Clin.Oncol.14. 497-502 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Semba S,et al: "Microsatellite instability in precancerous lesions and adenocarcinomas of the stomach." Cancer.77. 1620-1627 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Baba,H.,et al: "Two isotypes of murine nm23/nucleoside diphosphatekinase, nm23-M1 and nm23-M2, are involved in metastatic suppression of a murine melanoma line." Cancer Res.55. 1977-1981 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yamashiro,S.,et al: "Substrate specificity of b1.4N-acetylgalactosaminyltransferase in vitro and in cDNA-transfected Cells. GM2/GD2 synthase efficietly gene vates asialc GM2 in certain cells." J. Biol. Chem.270. 6149-6155 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Morishita,K.,et al: "EVI-1 2inc finger protein works as a transcriptional activator via binding a to consensus sequence of GACAAGATAAGATAA N1-28 CTCAT CTTC." Oncogene.10. 1961-1967 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Nishio,M.,et al.: "Prognostic significance of abnormal p53 accumulation in primary, resected non-small lung cancers." J. Clin. Oncol.(in press).

    • Related Report
      1995 Annual Research Report
  • [Publications] Yoshimura,M.,et al: "Suppression of lung metastasis of B16 mouse melanama by N-acetylglucosaminyltransferase III gene transfection." Proc. Natl. Acad. Sci. USA. 92. 8754-8758 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Miyoshi,E.,et al: "TGFb up-regulates expression of the N-acetylglucosaminyltransfernse V gene in mouse melanoma cells" J. Biol. Chem.270. 6216-6220 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Okada,K.,et al: "Isolation of human nm23 genomes and analysis of loss of heterozygosity in primary coloretal carcinomas using a specific genomic probe." Cancer Res. 54. 3979-3982 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Haraguchi,M.,et al: "Isolation of G_<D3> synthase gene by expression cloning of G_<M3> α-2,8-sialytransferase cDNA using anti-G_<D2> monoclomal antibody." Proc.Natl.Acad.Sci.USA. 91. 10455-10459 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Horii,A.,et al: "Frequent reprication errors at microsatellite loci in tumors of patients with multiple primary cancers" Cancer Res. 54. 3373-3375 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Suzukawa,K.,et al: "Identification of a breakpoint cluster region 3' of the transcriptional activation of the EVI-1 gene in acute myelogenous leukemias with inv (3) (q21q26)" Blood. 84. 2681-2688 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Suzuki,H.,et al.: "Altered imprinting in lung Cancer." Nature Genet. 6. 332-333 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Ikeda Y.,et al: "Expression of an active glycosylated human γ-glutamyltranspeptidase mutant that lacks a membrane anchor domain." Proc. Natl.Acad.Sci.USA. 92. 126-130 (1994)

    • Related Report
      1994 Annual Research Report

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

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