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Molecular analysis of traditional serrated adenoma as a candidate precursor of alternative serrated pathway

Research Project

Project/Area Number 16K09304
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Gastroenterology
Research InstitutionKanazawa University

Principal Investigator

Sawada Takeshi  金沢大学, 附属病院, 医員 (60345626)

Co-Investigator(Kenkyū-buntansha) 山本 英一郎  札幌医科大学, 医学部, 講師 (60567915)
Research Collaborator Suzuki Hiromu  札幌医科大学, 分子生物学講座, 教授 (20381254)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000)
Fiscal Year 2017: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords大腸癌 / 大腸鋸歯状腺腫 / 遺伝子メチル化 / 遺伝子変異 / Wntシグナル経路
Outline of Final Research Achievements

To clarify the molecular and clinicopathological characteristics of colorectal serrated lesions, we examined the mutation and methylation of cancer-associated genes in 78 serrated lesions, including traditional serrated adenomas (TSAs) and sessile serrated adenomas (SSAs). The prevalence of mutations in genes associated with Wnt signaling pathway was significantly higher in TSAs than SSAs. In addition, SMOC1 methylation was detected in 54.1% of TSAs but in no SSAs. These results suggests the presence of distinct carcinogenic pathways of TSAs from other precursor lesions. Furthermore, we detected significant differences in clinicopathological and molecular variables between TSAs with KRAS or BRAF mutation, which may indicate the presence of separate carcinogenic pathways among TSAs.

Academic Significance and Societal Importance of the Research Achievements

本研究により、従来より想定されてきた大腸鋸歯状腺腫(TSA)を前癌病変とする発癌経路の存在が示された。また、他の鋸歯状病変と比較してWntシグナル経路の異常が大きく関与していることが明らかとなった。今後、大腸鋸歯状病変の進展・発育により形成されると考えられている高悪性度大腸癌と分子プロファイルを比較することにより、TSAから高悪性度大腸癌に至る新たな発癌経路が確立できる。また、予後不良の高悪性度大腸癌に対する分子標的治療の開発に応用できる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (3 results)

All 2018

All Presentation (3 results) (of which Int'l Joint Research: 1 results)

  • [Presentation] Integrative analysis of gene mutations and DNA methylation in colorectal serrated lesions.2018

    • Author(s)
      Sawada T, Nakanishi H, Kaizaki Y, Sasaki Y, Yamamoto E, Aoki H, Eizuka M, Takahashi N, Hasatani K, Kubota E, Kataoka H, Ota R, Yanase Y, Inagaki S, Yamada S, Minamoto T, Suzuki H, Sugai T.
    • Organizer
      United European Gastroenterology Week (UEGW) 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 大腸鋸歯状病変における、遺伝子変異、コピー数変化、DNAメチル化の統合解析2018

    • Author(s)
      澤田 武、中西宏佳、佐々木泰史、山本英一郎、青木敬則、永塚 真、高橋直樹、太田亮介、久保田英嗣、片岡洋望、源 利成、菅井 有、鈴木 拓.
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 大腸鋸歯状病変における遺伝子変異,メチル化の統合解析2018

    • Author(s)
      中西宏佳,澤田 武,海崎泰治,佐々木泰史,山本英一郎,青木敬則,永塚 真,高橋直樹,波佐谷兼慶,久保田英嗣,片岡洋望,太田亮介,稲垣聡子,山田真也,源 利成,鈴木 拓,菅井 有
    • Organizer
      第60回日本消化器病学会総会
    • Related Report
      2018 Annual Research Report

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Published: 2016-04-21   Modified: 2020-03-30  

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