DNAメチル化と正常大腸―特にfield cancerizationについて―  [in Japanese] DNA methylation in normal colon—especially about "field cancerization"  [in Japanese]

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Author(s)

    • 前田 修 Maeda Osamu
    • 名古屋大学大学院医学系研究科消化器疾患先端研究寄附講座 Advanced Research of Gastroenterology, Nagoya University Graduate School of Medicine
    • 大宮 直木 Ohymiya Naoki
    • 名古屋大学大学院医学系研究科消化器内科学 Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine
    • 後藤 秀実 Goto Hidemi
    • 名古屋大学大学院医学系研究科消化器内科学 Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine
    • 安藤 貴文 Ando Takafumi
    • 名古屋大学大学院医学系研究科消化器内科学 Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine
    • 石黒 和博 Ishiguro Kazuhiro
    • 名古屋大学大学院医学系研究科消化器疾患先端研究寄附講座 Advanced Research of Gastroenterology, Nagoya University Graduate School of Medicine
    • 渡辺 修 Watanabe Osamu
    • 名古屋大学大学院医学系研究科消化器内科学 Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine
    • 日比 陽子 Hibi Yoko
    • 名古屋大学大学院医学系研究科医療薬学 Department of Hospital Pharmacy, Nagoya University Graduate School of Medicine
    • 永井 拓 Nagai Taku
    • 名古屋大学大学院医学系研究科医療薬学 Department of Hospital Pharmacy, Nagoya University Graduate School of Medicine
    • 山田 清文 Yamada Kiyofumi
    • 名古屋大学大学院医学系研究科医療薬学 Department of Hospital Pharmacy, Nagoya University Graduate School of Medicine
    • 舩坂 好平 Funasaka Kohei
    • 名古屋大学大学院医学系研究科消化器内科学 Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine
    • 宮原 良二 Miyahara Ryoji
    • 名古屋大学大学院医学系研究科消化器内科学 Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine

Abstract

Field cancerizationまたはfiled defectは腫瘍周囲の非癌部の組織における生物学的な変化を指し重要な発癌メカニズムと考えられている.我々は大腸癌患者の正常粘膜においてDNAメチル化異常がみられるかどうかについてゲノムワイドに解析した.Methylated CpG island amplification microarray(MCAM)を用いて健常人の正常大腸粘膜と大腸癌患者の非癌部のメチル化状態を比較した.健常人の大腸粘膜と大腸癌患者の正常外観の非腫瘍部の4対のペアについてMCAMにおいてメチル化レベルが異なると判定された15遺伝子を抽出した.候補遺伝子についてバイサルファイトパイロシークセンス法を用いて定量的メチル化解析を行った.また大腸内視鏡生検50検体を用いてメチル化レベルを定量的に評価した.その結果,有意にメチル化レベルの異なる遺伝子を見出すことはできなかった.大腸癌の周囲粘膜におけるプロモーター領域の高メチル化を示す遺伝子は多くないと考えられた.

Phenomenon of field cancerization or field defect is biological change as premalignancy at non-cancerous region around tumor, which is considered to be an important mechanism of carcinogenesis. We evaluated whether normal appearing mucosa of colorectal cancer patients has aberrant DNA methylation in a genome-wide manner. We compared methylation status in normal colorectal mucosa of healthy persons and colorectal cancer patients using methylated CpG island amplification microarray (MCAM), and extracted candidate genes with difference in methylation levels between healthy persons and colorectal cancer patients. We extracted fifteen genes in which we judged to have difference of methylation using MCAM between four pairs of normal colorectal mucosa of healthy persons and normal appearing mucosa adjacent to colorectal cancer. We performed quantitative methylation analysis with bisulfite pyrosequencing for candidate genes extracted with MCAM for the four pairs of samples. We also estimated the methylation levels of the genes of 50 colorectal biopsy samples using quantitative methods. We did not find any genes that revealed significant difference in methylation levels between adjacent mucosa and healthy normal colon. Aberrant promoter hypermethylation in normal appearing mucosa adjacent to colorectal cancer is not considered to be common.

Journal

  • SEIBUTSU BUTSURI KAGAKU

    SEIBUTSU BUTSURI KAGAKU 56(1), 9-14, 2012

    Japanese Electrophoresis Society

Codes

  • NII Article ID (NAID)
    130004456515
  • Text Lang
    JPN
  • ISSN
    0031-9082
  • Data Source
    J-STAGE 
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