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ゲノム整列化チップによる染色体異常の検出と小児がん関連遺伝子の探索

Research Project

Project/Area Number 14657184
Research Category

Grant-in-Aid for Exploratory Research

Allocation TypeSingle-year Grants
Research Field Pediatrics
Research InstitutionThe University of Tokyo

Principal Investigator

井田 孔明 (2003-2004)  東京大学, 医学部附属病院, 助手 (60313128)

林 泰秀 (2002)  東京大学, 医学部附属病院, 講師 (30238133)

Co-Investigator(Kenkyū-buntansha) 添田 栄一  東京大学, 理化学研究所・基盤研究部, 副主任研究員 (00039330)
滝田 順子  東京大学, 医学部附属病院, 助手 (00359621)
井田 孔明  東京大学, 医学部附属病院, 助手 (60313128)
川口 裕之  東京大学, 医学部附属病院, 助手 (00313130)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
Keywordsneuroblastoma / 1p36欠失 / API2 / 白血病 / 癌抑制遺伝子 / microarray / BACコンティグ / BAF60C / P19INK4D / DFF45 / Gene Chip / KIF1B gene / PEX14 / Charcot-Marie Tooth disease type2
Research Abstract

我々はこれまでスクリーニングキットやBACとPACの染色体整列化法を開発し、ゲノム整列化チップの実用化をすすめてきた。今回は、小児がんの診断としての染色体異常の検出のためのチップ作製と、小児がん関連遺伝子の探索法を検討した。まず小児がん、遺伝病等の染色体異常、あるいは遺伝子発現の動的変化を細胞遺伝学的レベルで検索し、その構造変化を簡便、迅速に解明できるゲノム整列化チップについて検討した。小児白血病と固形腫瘍の、70株からゲノムDNAとmRNAを抽出し、標識して、検出感度を高めた特異性の高い診断マニュアル作成するために、1p36のバックコンティグより1Mbごとのマーカーを抽出し検討した。ついで、アフィメトリックス社のGene Chipを用いて、まず神経芽腫20株で発現プロファイルを検討して予測し、さらに新鮮腫瘍50例で検討したところ、clusteringにより予後良好群と不良群に分けられた。API2とP19INK4D遺伝子は予後良好群で高発現であり、BAF60C遺伝子は予後良好群で有意に低発現であった。さらに染色体1p35-36の整列化したBACの内D1S244領域の200個を用い、キアゲン カラムで精製したDNAを手動のアレイアーでスポットし、プローブとして正常細胞、D1S244に欠損を持つ神経芽腫細胞株(NB-1)を使用し、アフィメトリックス社のスキャナーで定量したところhomozygous deletionの領域がみいだされ、BAC上の遺伝子を5種同定した。現在白血病についてもGene Chipの検討を進め、これらの作整したチップとGene Chipの12,600遺伝子との相関についても検討を進め、小児がん関連遺伝子の探索とアレイチップの完成をめざしている。

Report

(3 results)
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (20 results)

All 2005 2004 Other

All Journal Article (3 results) Publications (17 results)

  • [Journal Article] In vitro drug resistance to imatinib and mutation of ABL gene in childhood Ph+ acute lymphoblastic leukemia.2005

    • Author(s)
      Kawaguchi H
    • Journal Title

      Leukemia Lymphoma 46・2

      Pages: 273-276

    • Related Report
      2004 Annual Research Report
  • [Journal Article] FLT3 mutations in the activation loop of tyrosine kinase domain are frequently found in infant acute lymphoblastic leukemia (ALL) with MLL rearrangement and pediatric ALL with hyperdiploidy.2004

    • Author(s)
      Taketani T
    • Journal Title

      Blood 103・3

      Pages: 1085-1088

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Gene expression profiling and identification of novel prognostic marker genes in neuroblastoma.2004

    • Author(s)
      Takita J
    • Journal Title

      Genes Chromosomes Cancer 40・2

      Pages: 120-132

    • Related Report
      2004 Annual Research Report
  • [Publications] Xinh PT: "The breakpoints at 1p36.3 detected with BAC/PAC probes in three MDS/AML(M4) patients with t(1;3)(p36;q21) translocation : in the first intron and in the 5' region of MEL1"Genes Chromosome Cancerr. 36・3. 313-317 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Terui, K: "Successful treatment of acute myelomonocytic leukaemia with NUP98-HOXD11 fusion transcripts and monitoring of minimal residual disease."Br.J.Haematol. 120・2. 274-276 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hiwatari M: "Fusion of an AF4-related gene, LAF4, to MLL in childhood acute lymphoblastic leukemia with t(2;11)(q11;q23)."Oncogene. 22・18. 2851-2855 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Taketani T: "AML1/RUNX1 mutations are infrequent, but related to AML-MO, acquired trisomy 21, and leukemic transformation in pediatric hematologic malignancies."Genes Chromosomes Cancer. 38・1. 1-7 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Echlin-Bell DR: "Polymorphisms in the MLL breakpoint cluster region (BCR)."Hum Genet. 113・1. 80-91 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Chen YY: "Genomic structure and mutational analysis of the human KIF1Balpha gene located at 1p36.2 in neuroblastoma."Int J Oncol. 23・3. 737-744 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Xu G: "Frequent mutations in the GATA-1 gene in the transient myeloproliferative disorder of Down syndrome."Blood. 102・8. 2960-2968 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tsutsumi S: "Two distinct gene expression signatures in pediatric acute lymphoblastic leukemia with MLL rearrangements."Cancer Res. 63・16. 4882-4887 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hirose Y: "Comprehensive analysis of gene alterations in acute megakaryoblastic leukemia of Down's syndrome."Leukemia. 17・11. 2250-2252 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Obana K: "Aberrations of p16INK4A, p14ARF and p15INK4B genes in pediatric solid tumors."Int J Oncol.. 23・4. 11511-11577 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Taketani T: "FLT3 mutations in the activation loop of tyrosine kinase domain are frequently found in infant acute lymphoblastic leukemia (ALL) with MLL rearrangement and pediatric ALL with hyperdiploidy."Blood. 103・3. 1085-1088 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Taketani T: "The HOXD11 gene is fused to the NUP98 gene in acute myeloid leukemia with the t(2;11)(q31;p15)"Cancer Res. 62. 33-37 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ono R: "SEPTIN6, a Human Homologue to Mouse Septin6, Is Fused to MLL in Infant Acute Myeloid Leukemia with Complex Chromosomal Abnormalities Involving 11q23 and Xq24"Cancer Res. 62. 333-337 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Uno K: "Aberrations of the hSNF5/INI1 gene are restricted to malignant rhabdoid tumors or atypical teratoid/rhabdoid tumors in pediatric solid tumors"Genes Chromosomes Cancer. 34. 33-41 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Taketani T: "The t(7;11)(p15;p15) in acute myeloid leukemia results in fusion of the NUP98 gene with a HOXA cluster gene, HOXA13, but not HOXA9"Genes Chromosomes Cancer. 34. 437-443 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ono R: "LCX, leukemia-associated protein with a CXXC domain, is fused to MLL in acute myeloid leukemia with trilineage dysplasia having t(10;11)(q22;q23)"Cancer Res. 62. 4075-4080 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Taketani T: "Novel NUP98-HOXC11 Fusion Gene Resulted from a Chromosomal Break within Exon 1 of HOXC11 in Acute Myeloid Leukemia with t(11;12)(p15;q13)"Cancer Res. 62. 4571-4574 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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