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Intratumoral Heterogeneity of Sporadic Colorectal Cancer using Crypt Isolation Technique

Research Project

Project/Area Number 10670171
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Human pathology
Research InstitutionIwate Medical University

Principal Investigator

NAKAMNRA Shin-ich  IWATE MEDICAL UNIVERSITY, 医学部, 教授 (20107816)

Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1999: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1998: ¥2,900,000 (Direct Cost: ¥2,900,000)
KeywordsCrypt isolation / Colorectal cancer / intratumor heterogeneity / MLH1 / MSH2 / Mismatch repair gene / LOH / Microsatellite instability / フローサイトメータ
Research Abstract

Tumor suppressor gene mutat ions such as ABC or p.53 have been considered to play an important role in colorectal carcinogenesis. Recently, DNA replication error phenotype has also found to play a key role in colorectal carcinogenesis.
In order to determine the effects of mismatch repair (MMR) (deficiencics in sporadic colorectal carcinomas, 45 such cancers were examined using a sensitive method called crypt. Isolation technique. Loss of heterozygosity (LOH) in the MSH2 or MLHl gene was more frequently observed in replication error (RER) (+) carcinomas than in RER (-) carcinomas, which implied that loss of one normal allele could partly affect repair capacity. MSH2 gene (defects at both alleles were observed in two carcinomas, which showed severe repair deficiencies. Interestingly, unlike the situation observed in the p53 gene, the MSH2 and MLH1 genes did not show complete LOH. Novel crypt isolation-based subpopulation (CISP) analysis demonstrated that at least two distinct carcinoma suhpopulation existed in most carcinomas that showed incomplete LOH; one with and one wihiout LOH. In one carcinoma that tad germline.ine mutation and somatic incomplete LOB of the MSH2 gene, the mutator phenotype was only observed in population affected in both alleles. Thus, the MSH2 gene appears to possess the two hits mechanism of tumor suppressor genes. However, unlike the tumor suppressor gene, MMR gene defects lead to a unique mode of colorectal tumorigenesis characterized by intratumoral heterogeneity.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Habano W, Sugai T, Nakamura S.: "Mismatch repair deficiency leads to a unique mode of colorectal tumorigenesis characterized by intratumoral heterogeneity"Oncogene. 16. 1259-1265 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Habano W, Nakamura S, Sugai T.: "Microsatellite instability in the mitochondrial DNA of colorectal carcinomas: Evidence for mismatch repair systems in mitochondrial genome"Oncogene. 17. 1931-1937 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sugai T, Nakamura S, Habano W, Uesugi N, Sato H, Funato O, Sasou S, Orii S, Itoh C: "Analysis of subclonal expansion of colorectal carcinomas by flow cytometry"Virchows Arch. 434. 437-441 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sugai T, Nakamura S, Habano W, Uesugi N, Sato H, Yoshida T, Orii S,: "Usefulness of proliferative activity, DNA ploidy pattern and p53 products as diagnostic adjuncts in colorectal adenomas and intramucosal carcinomas."Pathology International. 49. 617-625 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sugai T. Nakamura S, Uesugi N, Habano W, Yoshida T, Tazawa H, Orii S, Suto T, Itoh C.: "Role of DNA aneuploidy, overexpression of p53 gene product, and cellular proliferation in the progression of gastric cancer"Cytometry. 38. 111-117 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Habano W, Sugai T, Yoshida T, Nakamura S.: "Mitochondrial gene mutation, but not large-scale deletion, is a feature of colorectal carcinomas with mitochondrial microsatellite instability"Int. J. Cancer. 83. 625-629 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kitayama Y, Nakamura S, Sugimura H, Kino I.: "Cytophotometric and flow cytometric DNA content of isolated glands in gastric neoplasia."Gut. 36. 516-521 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Habano W, Sugai T, Nakamura S, Yoshida T.: "A novel method for gene analysis of colorectal carcinomas using a crypt isolation technique."Lab Invest. 74. 933-940 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yoshida T, Nakamura S, Sugai T.: "DNA ploidy and S-phase fraction of neoplastic and non-neoplastic lesions of the human gallbladder."J Surg Oncol. 63. 9-16 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Suto T, Sugai T, Nakamura S. Uesugi N, Sasaki R, Kanno S, Saito K: "Immunochemical detection of proliferative cell nuclear antigen and p53 expression in carcinoma of the extrahepatic bile duct."Oncology. 54. 407-413 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Suto T. Sugai T, Nakamura S, Funato 0, Nitta H, Sasaki R, Nanno S, Saito K: "Assessment of the expression of p53, NIB-1 (ki-67antigen) , and argyrophilic nucleolar organizer regions in carcinoma of the extrahepatic. Bile duct."Cancer. 82. 86-95 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Habano W, Sugai T, Nakamura S: "Mismatch repair deficiency leads to a unique mode of colorectal tumorigenesis characterized by intratumoral heterogeneity."Oncogene. 16. 1259-1265 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sngai T, Habano W, Nakamura S, Yoshida T, Uesugi N, Suto T, Ito C: "Correlation of histologic morphology and tumor stage with molecular genetic analysis using microdissection in gastric carcinomas."Diagnostic Molecular Pathology. 7. 235-240 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Habano W. Nakamura S, Sugai T: "Microsatellite instability in the mitochondrial DNA of colorectal calcinomas: Evidence for mismatch repair systems in mitochondral genome"Oncogene. 17. 1931-1937 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sugai T, Nakamura S, Habano W, Uesugi N, Sato H, Funato 0. Sasou S. Orri S. Itoh C: "Analysis of subclonal expansion of colorectal carcinomas by flow cytometry."Virchows Arch. 434. 437-441 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sugai T, Nakamura S, Habano W, Uesugi N, Sato H, Yoshida T, Orri S: "Usefulness of proliferative activity, DNA ploidy pattern and p53 products as diagnostic adjuncts in colorectal adenomas and intramucosa1 carcinomas."Pathology International. 49. 617-625 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sugai T, Nakamura S, Uesugi N, Habano W, Yoshida T, Tazawa H, Orri S. Suto T, Itoh C: "Role of DNA aneuploidy, overexpression of p53 gene product, and cellular proliferation in the progression of gastric cancer."Cytometry. 38. 111-117 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Habano W, Sugai T, Yoshida T, Nakamura S: "Mitochondrial gene mutation, but not large-scale deletion, is a Feature of colorectal carcinomas with mitochondrial microsatellite instability."Int J Cancer. 83. 625-629 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Habano W,Sugai T,Nakamura S,Yoshida T: "A novel method for gene analysis of coloerctal carcinomas using a cryptisolation technique."Lab Invest. 74. 933-940 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Habano W,Sugai T,Nakamura S: "Mismatch repair deficiency leads to a unique mode of colorectal tumorigenesis characterized by intratumoral heterogeneity"Oncogene. 16. 1259-1265 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Habano W,Nakamura S,Sugai T: "Microsatellite instability in the mitochondrial DNA of colorectal carcinomas:Evidence for mismatch repair systems in mitochondrial genome"Oncogene. 17. 1931-1937 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Habano W,Sugai T,Nakamura S,Yoshida T: "A novel method for gene analysis of colorectal carcinomas using a crypt isolation technique." Lab Invest. 74. 933-940 (1996)

    • Related Report
      1998 Annual Research Report
  • [Publications] Habano W,Sugai T,Nakamura S: "Mismatch repair deficiency leads to a unique mode of colorectal tumorigenesis characterized by intratumoral heterogeneity" Oncogene. 16. 1259-1265 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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