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Methylation of mismatch repair gene and E-cadherin gene abnormality in serrated adenoma of the colorectum

Research Project

Project/Area Number 13670167
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Human pathology
Research InstitutionNIIGATA UNIVERSITY

Principal Investigator

AJIOKA Yoichi  NIIGATA UNIVERSITY Graduate School of Medical and Dental Sciences, Associate Professor, 大学院・医歯学総合研究科, 助教授 (80222610)

Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2001: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywordscolorectal adenoma / serrated adenoma / APC / E-cadherin / hMLH1 / methylation / gene alteration / mucus phenotype / MSI / hMLH1
Research Abstract

APC, E-cadherin gene mutation and methylation and hMLH1 gene methylation, and mucus phenotype of colorectal serrated adenoma (SA) were investigated and compared with those of tubular adenoma (TA).
1. APC : Both mutation (exon 1 to 7) and methylation rate of SA [3% (1/34), 19.2% (5/23)] were significantly lower that those of TA [40% (4/10), 90% (9/10)] (p<0.005).
2. E-cadherin : No significant difference was found in mutation (exon 6-9) and methylation rate between SA [6% (2/34), 68% (23/24)] and TA [0% (0/10), 50% (5/10)]. Mutation found in SA was identical with that found in gastric carcinoma with gastric mucus phenotype (18-base pair deletion of codon 418 to 423).
3. hMLH1: methylation was found in 88% (30/34) of SA.
4. Mucus phenotype: Although there was no significant difference in MUC5AC expression between SA[93.5% (29/31)] and TA[90.5% (19/21)], MUC6 was highly expressed in SA[71% (22/31)] than TA[14.3% (3/21)] (p<0.0001).
5. Conclusion and Discussion : APC and E-cadherin alterations would not play a role in the development of SA. Role of abnormality in hMLH1 remained to be elucidated. Expression of MUC6 (gastric pyloric type core protein) was the characteristic phenotype of SA. Identical mutational pattern seen in SA and gastric carcinoma with gastric phenotype suggested a possibility that neoplasia with gastric mucus phenotype, regardless of organ, may be involved in common genetic alterations.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] Endo Y: "Cellular phenotype of differentiated-type adenocarcinomas and precancerous lesions of the stomach are dependent on genetic pathway"J Pathology. 191. 257-263 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ajioka Y: "Early colorectal cancer with special reference to the superficial nonpolypoid type"World J Surgery. 24. 1075-1080 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Endo Y: "Frequent hypermethylation of the hMLH1 gene promoter in differentiated type tumors of the stomach with gastric phenotype"Am J Pathology. 157. 717-722 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamada S: "Heterogeneity of p53 mutational status in intramucosal carcinoma of the colorectum"Jpn J Cancer Res. 92. 161-166 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fujii H: "Loss of heterozygosity in the clonal evolution of flat colorectal neoplasms"J Pathology. 197. 298-306 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Komori K: "Proliferation kinetics and apoptosis of serrated adenoma of the colorectum"Pathology Int. 53. 277-283 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Endo Y, Sakata K, Tamura G, Ohmura K, Ajioka Y, Watanabe H, Motoyama T: "Cellular phenotypes of differentiated-type adenocarcinomas and precancerous lesions of the stomach are dependent on the genetic pathways"J Pathol. 191. 257-263 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ajioka Y, Watanabe H, Kazama S, Hashidate H, Yokoyama J. Yamada S, Takaku H, Nishikura K: "Early colorectal cancer with special reference to the superficial nonpolypoid type from a histopathologic point of view"World J Surg. 24. 1075-1080 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Endo Y, Tamura G, Ajioka Y, Watanabe H, Motoyama T: "Frequent hypermethylation of the hMLH1 gene promoter in differentiated-type tumors of the stomach with the gastric foveolar phenotype"Am J Pathol. 157. 717-722 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamada S, Ajioka Y, Watanabe H, Hashidate H, Takaku H, Kazama S, Yokoyama J, Nishikura K, Fujiwara T, Asakura H: "Heterogeneity of p53 mutational status in intramucosal carcinoma of the colorectum"Jpn J Cancer Res. 92. 161-166 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fujii H, Ajioka Y, Kazama S, Takagaki T, Zhu XG, Hirose S, Watanabe H, Shirai T: "Loss of heterozygosity in the clonal evolution of flat colorectal neoplasms"J Pathology. 197. 298-306 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Komori K, Ajioka Y, Watanabe H, Oda K, Nimura Y: "Proliferation kinetics and apoptosis of serrated adenoma of the colorectum"Pathology Int. 53. 277-283 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fujii H: "Loss of heterozygosity in the clonal evolution of flat colorectal neoplasms"J Pathology. 197. 298-306 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Koji K: "Proliferation kinetics and apoptosis of serrated adenoma of the colorectum"Pathology International. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Endo Y.: "Cell ular pheustype of differentialted-type adenciarcinomced and precancerous lesions of the Jtomach as dependent on the genetic pay riony"J Pathology. 191. 257-263 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kobayashi M.: "Nuclear translocation of beta-catonia in coloreiti cancer"Brit J Cancer. 82. 1689-1693 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ajioka Y.: "Early colorectal cancer with special reference to the superficial nonpolypoid type from a histopathologic point of view"World J surg. 24. 1075-1080 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Endo Y.: "Frogaent Rypermothylation F the mlmlgene promoter in different type camera of the stomach the with the garthie phemtype"Am J physiology. 157. 717-722 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takaku M.: "Mutations of P53 in mophelogiency non-neoplath mycasa of long-standing ulcelative volitis"Jpn J Cancer Ros. 92. 119-126 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamada S.: "Metemogenafy of 053 mutadionet status in intramylojgl carinome of the calorectym"Jpn J Cancer Ros. 92. 161-166 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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