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Genome-wide analysis of intratumoral heterogeneity in genomic copy number and expression pattern.

Research Project

Project/Area Number 15590301
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Human pathology
Research InstitutionShiga University of Medical Science

Principal Investigator

SUGIHARA Hiroyuki  Shiga University of Medical Science, Faculty of Medicine, Associate Professor, 医学部, 助教授 (30171169)

Co-Investigator(Kenkyū-buntansha) MUKAISHO Ken-ichi  Shiga University of Medical Science, Faculty of Medicine, Research Assistant, 医学部, 助手 (50343223)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
KeywordsGastric carcinoma / Laser microdissection / DOP-PCR / CGH / cDNA microarray / CESH / Intratumoral heterogeneity / 食道癌 / 未分化型胃癌 / array CGH / cDNA microarray / LOH解析 / 遺伝子診断 / ゲノム不安定性
Research Abstract

This study focused on the problems ; to what extent the regional heterogeneity of the gene expression pattern is ascribed to the regional changes in genomic copy number and to what extent the gene expression pattern of the deep invasion is inferred from the mucosal biopsy specimen.
Using gastric carcinoma(GC) cell lines and primary esophageal and gastric carcinomas, we carried out comparative genome-wide analyses of the transcription pattern and the genomic copy number at the chromosome level, which were determined by comparative expressed sequence hybridization(CESH) and comparative genomic hybridization(CGH), respectively. We firstly established the methodology of CESH that showed better concordance with the results of cDNA microarray by modifying the methods of probe labeling and those of signal amplification. We found that the concordance with CDNA microarray was higher in T7 amplification and pre-cDNA labeling than in the DOP-PCR amplification/labeling that was previously used for … More CESH.
Secondly, using two cell lines deriving from undifferentiated-type GC, we demonstrated that gene expression was often up/down-regulated in clustered genes in certain chromosomal loci that can be detected by CESH as well as cDNA microarray and that these expression changes may have resulted either from genomic copy number changes or from transcriptional regulation. Thirdly, using multiple samples from individual primary GCs and esophageal cancers, the stemline copy-number changes that were consistently detected in multiple samples were mostly found to accompany up/down-regulation of the corresponding chromosomal segments. About 50% of stemline up/down-regulations were accompanied by genomic copy number changes, whereas heterogeneous up/down-regulations were infrequently accompanied by the genomic changes.
These findings suggest that we may infer the gene expression pattern in the deeper part of the tumor from that in the mucosa only in the chromosomal regions of stemline changes that are determined from multiple mucosal samples. Less

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (15 results)

All 2005 2004 2003 Other

All Journal Article (13 results) Publications (2 results)

  • [Journal Article] Effects of degenerate oligonucleotide-primed polymerase chain reaction amplification and labeling methods on the sensitivity and specificity of metaphase- and array-based comparative genomic hybridization.2005

    • Author(s)
      Tsubosa Y, et al.
    • Journal Title

      Cancer Genetics and Cytogenetics 158

      Pages: 156-166

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 未分化型胃癌の系譜解析2005

    • Author(s)
      杉原 洋行
    • Journal Title

      Cytometry Research 15

      Pages: 47-53

    • NAID

      10016787792

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effects of degenerate oligonucleotide-primed polymerase chain reaction amplification and labeling methods on the sensitivity and specificity of metaphase-and array-based comparative genomic hybridization.2005

    • Author(s)
      Tsubosa Y, et al.
    • Journal Title

      Cancer Genetics and Cytogenetics 158(2)

      Pages: 156-166

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Lineage analyses of undifferentiated-type gastric carcinomas.2005

    • Author(s)
      Sugihara H.
    • Journal Title

      Cytometry Research 15(1)

      Pages: 47-53

    • NAID

      10016787792

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effects of degenerate oligonucleotide-primed polymerase chain reaction (DOP-PCR) amplification and labeling methods on the sensitivity and specificity of metaphase- and array-based comparative genomic hybridization.2005

    • Author(s)
      Tsubosa Y, Sugihara H, et al.
    • Journal Title

      Cancer Genetics and Cytogenetics (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 未分化型胃癌の系譜解析2005

    • Author(s)
      杉原 洋行
    • Journal Title

      Cytometry Research (in press)

    • NAID

      10016787792

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Genetic lineage of poorly differentiated gastric carcinoma with tubular component analysed by comparative genomic hybridization.2004

    • Author(s)
      Peng D-F, et al.
    • Journal Title

      Journal of Pathology 203

      Pages: 884-895

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Genetic lineage of poorly differentiated gastric carcinoma with tubular component analysed by comparative genomic hybridization.2004

    • Author(s)
      Peng D-F, et al.
    • Journal Title

      Journal of Pathology 203(8)

      Pages: 884-895

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Genetic lineage of poorly differentiated gastric carcinoma with tubular component analysed by comparative genomic hybridization.2004

    • Author(s)
      Peng D-F, Sugihara H, et al.
    • Journal Title

      Journal of Pathology 203(8)

      Pages: 884-895

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Cytogenetic heterogeneity and progression of esophageal squamous cell carcinoma.2003

    • Author(s)
      Shiomi H, et al.
    • Journal Title

      Cancer Genetics and Cytogenetics 147

      Pages: 50-61

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Alterations of chromosomal copy number during progression of diffuse-type gastric carcinomas : metaphase- and array-based comparative genomic hybridization analyses of multiple samples in individual tumors.2003

    • Author(s)
      Peng D-F, et al.
    • Journal Title

      Journal of Pathology 201

      Pages: 439-450

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Cytogenetic heterogeneity and progression of esophageal squamous cell carcinoma.2003

    • Author(s)
      Shiomi H, et al.
    • Journal Title

      Cancer Genetics and Cytogenetics 147(1)

      Pages: 50-61

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Alterations of chromosomal copy number during progression of diffuse-type gastric carcinomas : metaphase-and array-based comparative genomic hybridization analyses of multiple samples in individual tumours.2003

    • Author(s)
      Peng D-F, et al.
    • Journal Title

      Journal of Pathology 201(3)

      Pages: 439-450

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Peng D-F, Sugihara H et al.: "Alterations of chromosomal copy number during progression of diffuse-type gastric carcinomas : metaphase- and array-based comparative genomic hybridization analyses of multiple samples in individual tumors"The Journal of Pathology. 201・3. 439-450 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shiomi H, Sugihara H et al.: "Cytogenetic heterogeneity and progression of esophageal squamous cell carcinoma"Cancer Genetics and Cytogenetics. 147・1. 50-61 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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