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Investigation of genetic alteration and molecular basis of de novo colorectal cancer

Research Project

Project/Area Number 26860518
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Gastroenterology
Research InstitutionYokohama City University

Principal Investigator

SAKAI Eiji  横浜市立大学, 医学(系)研究科(研究院), 客員研究員 (30600233)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords大腸癌 / 遺伝子変異 / 大腸発癌 / DNAメチル化 / de novo癌 / LST
Outline of Final Research Achievements

In this study, we revealed molecular basis of laterally spreading tumor (LST), using genome-wide comprehensive analyses. Firstly, we assessed their epigenetic background. Subsequently, we conducted targeted exon sequencing including 38 candidate CRC driver genes. By hierarchical clustering using methylation information, LST was clearly classified into two subtypes; LST-G correlating to IME, and LST-NG correlating to LME. Genes associated with RTK/RAS signaling pathway were mutated more frequently in LST-G than LST-NG (P=0.004), especially KRAS mutation. Both LSTs showed high frequency of APC mutation even at adenoma stage, suggesting its involvement in initiation stage of LST, like adenoma-carcinoma sequence. TP53 mutation was specifically detected in cancer samples. TP53 mutation occurred during development of intramucosal cancer in LST-NG, but during development of cancer with submucosal invasion in LST-G, suggesting involvement of TP53 mutation at earlier stage in LST-NG.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (2 results)

All 2016 2015

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (1 results)

  • [Journal Article] TP53 mutation at early stage of colorectal cancer progression from two types of laterally spreading tumors.2016

    • Author(s)
      Sakai E, Fukuyo M, Matsusaka K, Ohata K, Doi N, Takane K, Matsuhashi N, Fukushima J, Nakajima A, Kaneda A
    • Journal Title

      Cancer Science

      Volume: 印刷中 Issue: 6 Pages: 820-7

    • DOI

      10.1111/cas.12930

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] DNAメチル化マーカーおよび癌遺伝子パネル解析を用いた大腸LSTの分子生物学的背景の解明2015

    • Author(s)
      酒井英嗣,金田篤志,中島淳
    • Organizer
      第101回 消化器病学会 総会 仙台 パネルディスカッション 17
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2015-04-23
    • Related Report
      2015 Annual Research Report

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Published: 2014-04-04   Modified: 2017-05-10  

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