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2000 Fiscal Year Final Research Report Summary

Genome analysis of the neuroblastoma-related regions in 1p36

Research Project

Project/Area Number 11670808
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionChiba Cancer Center Research Institute

Principal Investigator

ICHIKAWA-OHIRA Miki (大平 美紀)  Chiba Cancer Center Research Institute, Division of Biochemistry, Research Fellow, 研究局・生化学研究部, 研究員 (20311384)

Co-Investigator(Kenkyū-buntansha) KAGEYAMA Hajime  Chiba Cancer Center Research Institute, Division of Biochemistry, Research Fellow, 研究局・生化学研究部, 研究員 (50260253)
NAKAGAWARA Akira  Chiba Cancer Center Research Institute, Division of Biochemistry, Head, 研究局・生化学研究部, 部長 (50117181)
Project Period (FY) 1999 – 2000
Keywords1p36 / Neuroblastoma / homozygous deletion / positional cloning / tumor suppressor gene
Research Abstract

Loss of heterozygosity of the distal region of chromosome 1p where tumor suppressor gene(s) might harbor is frequently observed in many human cancers including neuroblastoma(NBL)with MYCN amplification and poor prognosis. We have identified for the first time a homozygously deleted region at the marker D1S244 within the smallest region of overlap at 1p36.2-p36.3 in two NBL cell lines, NB-1 and NB-C201(MASS-NB-SCH1), although our genotyping has suggested the possibility that both lines are derived from the same origin. The 800-kb PAC contig covering the entire region of homozygous deletion was made and partially sequenced(about 60%). The estimated length of the deleted region was 500-kb. We have, thus far, identified 6 genes within the region which include three known genes(DEF45, PGD, and CORT)as well as three other genes which have been reported during processing our present project for the last 3 years and a half(HDNB1/UFD2, KIAA0591F/K1F1B-β, and PEX14). They include the genes related to apoptosis, glucose metabolism, ubiquitin-proteasome pathway, a neuronal microtubule-associated motor molecule and biogenesis of peroxisome. At least three genes(HDNB1/UFD2, KIAA0591F/KIF1B-β, and PEX14)were differentially expressed at high levels in favorable and at low levels in unfavorable subsets of primary neuroblastoma. Since the 1p distal region is reoported to be imprinted, those differentially expressed genes could be the new members of the candidate NBL suppressor, although RT-PCR-SSCP analysis has demonstrated infrequent mutation of the genes so far identified. Full-sequencing and gene prediction for the region of homozygous deletion would elucidate more detailed structure of this region and might lead to discovery of additional candidate genes.

  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] Ohira M, Shishikura T, et al.: "Hunting the subset-specific genes of neuroblastoma : expression profiling and differential screening of the full-length-enriched oligo-capping cDNA libraries."Med. Pediatr. Oncol.. 35. 547-549 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawamoto T, Ohira M, et al.: "Association between favorable neuroblastoma and high expression of the novel metalloproteinase gene, nbla3145/XCE, cloned by differential screening of the full-length-enriched oligo-capping neuroblastoma cDNA libraries."Med. Pediatr. Oncol.. 35. 628-631 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakagawara A, Ohira M, et al.: "Identification of the homozygously deleted region at chromosome 1p36.2 in human neuroblastoma."Med. Pediatr. Oncol.. 35. 516-521 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Furuta S, Ohira M, et al.: "Analysis of loss of heterozygosity at 16p12-p13 (familial neuroblastoma locus) in 470 neuroblastomas including both sporadic and mass screening tumors."Med. Pediatr. Oncol.. 35. 531-533 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ohira M, Kageyama H, et al.: "Identification and characterization of a 500-kb homozygously deleted region at 1p36.2-p36.3 in a neuroblastoma cell line."Oncogene. 19. 4302-4307 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nagai M, Ohira M, et al.: "Identification of the full-length KIAA0591 gene encoding a novel kinesin-related protein which is mapped to the neuroblastoma suppressor gene locus at 1p36.2."Int. J. Oncol.. 16. 907-916 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Islam A, Ohira M, et al.: "High expression of Survivin, mapped to 17q25, is significantly associated with poor prognostic factors and promotes cell survival in human neuroblastoma."Oncogene. 19. 617-623 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hanaoka E, Ohira M, et al.: "Molecular cloning and expression analysis of the human DA41 gene and its mapping to chromosome 9q21.2-q21.3. "J Hum Genet.. 45. 188-191 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ozaki T, Ohira M, et al.: "NFBD1/KIAAO170 is a novel nuclear transcriptional transactivator with BRCT domain. "DNA Cell Biol.. 19. 475-485 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ichimiya, S. , Ohira, M. et al.: "p73 at chromosome 1p36.3 is lost in advanced stage neuroblastoma but its mutation is infrequent."Oncogene. 18. 1061-1066 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Seki, N. , Ohira, M. et al.: "Chromosomal assignment of a human apoptosis-associated tyrosine kinase gene on chromosome 17q25.3 by somatic hybrid analysis and fluorescence in situ hybridization."J. Hum. Genet.. 44. 141-142 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ueki, N. , Ohira, M. et al.: "Isolation and chromosomal assignment of human genes encoding cofactor of LIM homeodomain proteins, CLIM1 and CLIM2."J. Hum. Genet.. 44. 112-115 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Seki, N. , Ohira, M. et al.: "Structure, expression profile and chromosomal location of an isolog of DNA-PKcs interacting protein (KIP) gene 1."Biochim. Biophys. Acta. 1444. 143-147 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ohira M, Shishikura T, Kawamoto T, Inuzuka H, Morohashi A, Takayasu H, Kageyama H, Takada N, Takahashi M, Sakiyama S, Suzuki Y, Sugano S, Kuma H, Nozawa I, Nakagawara A.: "Hunting the subset-specific genes of neuroblastoma : expression profiling and differential screening of the full-length-enriched oligo-capping cDNA libraries"Med. Pediatr. Oncol.. 35. 547-9 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kawamoto T, Shishikura T, Ohira M, Takayasu H, Morohashi A, Takada N, Takahashi M, Suzuki Y, Sugano S, Hori T, and Nakagawara A.: "Association between favorable neuroblastoma and high expression of the novel metalloproteinase genem, nbla3145/XCE, cloned by differential screening of the full-length-enriched oligo-capping neuroblastoma cDNA libraries"Med. Pediatr. Oncol. 35. 628-31 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakagawara A, Ohira M, Kageyama H, Mihara M, Furuta S, Machida T, Takayasu H, Islam A, Nakamura Y, Takahashi M, Shishikura T, Kaneko Y, Toyoda A, Hattori M, Sakaki Y, Ohki M, Horii A, Soeda E, Inazawa J, Seki N, Kuma H, Nozawa, I, and Sakiyama S: "Identification of the homozygously deleted region at chromosome 1p36.2 in human neuroblastoma."Med. Pediatr. Oncol. 35. 516-21 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Furuta S, Ohira M, Machida T, Hamano S, and Nakagawara A.: "Analysis of loss of heterozygosity at 16p12-p13(familial neuroblastoma locus)in 470 neuroblastomas including both sporadic and mass screening tumors."Med. Pediatr. Oncol.. 35. 531-3 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ohira M, Kageyama H, Mihara M, Furuta S, Machida T, Shishikura T, Takayasu H, Islam A, Nakamura Y, Takahashi M, Tomioka N, Sakiyama S, Kaneko Y, Toyoda A, Hattori M, Sakaki Y, Ohki M, Horii A, Soeda E, Inazawa J, Seki N, Kuma H, Nozawa I, and Nakagawara A.: "Identification and characterization of a 500-kb homozygously deleted region at 1p36.2-p36.3 in a neuroblastoma cell line"Oncogene. 19. 4302-7 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nagai M, Ichimiya S, Ozaki T, Seki N, Mihara M, Furuta S, Ohira M, Tomioka N, Nomura N, Sakiyama S, Kubo O, Takakur K, Hori T, and Nakagawara A.: "Identification of the full-length KIAA0591 gene encoding a novel kinesin-related protein which is mapped to the neuroblastoma suppressor gene locus at lp36.2"Int. J.Oncol.. 16. 907-16 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Islam A.Kageyama H, Takada N, Kawamoto T, Takayasu H, Isogai E, Ohira M, Hashizume K, Kobayashi H, Kaneko Y, and Nakagawara A.: "High expression of Survivin, mapped to 17q25, is significantly associated with poor prognostic factors and promotes cell survival in human neuroblastoma."Oncogene. 19. 617-23 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hanaoka E, Ozaki T, Ohira M, Nakamura Y, Suzuki M, Takahashi E, Moriya H, Nakagawara A, and Sakiyama S.: "Molecular cloning and expression analysis of the human DA41 gene and its mapping to chromosome 9q21.2-q21.3"Hum Genet.. 45. 188-91 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ozaki T, Nagase T, Ichimiya S, Seki N, Ohira M, Nomura N, Takada N, Sakiyama S, Weber BL, and Nakagawara A.: "NFBD1-KIAA0170 is a novel nuclear transcriptional transactivator with BRCT domain."DNA Cell Biol.. 19. 475-85 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ichimiya, S., Nimura, Y., Kageyama, H., Takada, N., Sunahara, M., Shishikura, T., Nakamura, Y., Sakiyama, S., Seki, N., Ohira, M., Kaneko, Y., McKeon, F., Caput, D., and Nakagawara, A.: "p73 at chromosome lp36.3 is lost in advanced stage neuroblastoma but its mutation is infrequent."Oncogene. 18. 1061-1066 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Seki, N., Hayashi, A., Hattori, A., Kozuma, S., Ohira, M., Hori, T., and Saito, T.: "Choromosomal assignment of a human apoptosis-associated tyrosine kinase gene on chromosome 17q25.3 by somatic hybrid analysis and fluorescence in situ hybridization."J.Hum. Genet. 44. 141-142 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ueki, N., Seki, N., Yano, K., Ohira, M., Saito, T., Masuho, Y., and Muramatsu, M.: "Isolation and chromosomal assignment of human genes encoding cofactor of LIM homeodomain proteins, CLIM1 and CLIM2."J.Hum. Genet. 44. 112-115 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Seki, N., Hattori, A., Hayashi, A., Kozuma, S., Ohira, M., Hori, T., Saito, T.: "Structure, expression profile and chromosomal location of an isolog of DNA-PKcs interacting protein(KIP)genel."Biochim. Biophys. Acta.. 1444. 143-147 (1999)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2002-03-26  

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