2019 Fiscal Year Final Research Report

Analysis of the profile in DNA methylation alterations to predict susceptibility to cancer development

Research Project

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Project/Area Number	16K10548
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Digestive surgery
Research Institution	Jichi Medical University
Principal Investigator	Rikiyama Toshiki 自治医科大学, 医学部, 教授 (80343060)
Co-Investigator(Kenkyū-buntansha)	鈴木浩一自治医科大学, 医学部, 准教授 (70332369)
Project Period (FY)	2016-04-01 – 2020-03-31
Keywords	癌易罹患性 / DNAメチル化プロファイル / 遺伝子修飾異常 / 遺伝子異常 / 非癌部組織 / DNAメチル化マイクロアレイ / MS-AFLP microarray
Outline of Final Research Achievements	The aim of this study is to predict susceptibility to cancer development on the basis of the epigenetic profile observed in non-cancerous mucosa. Epigenetic alterations are commonly observed not only in cancer tissues but also in non-cancerous tissues, whereas genetic alterations are found in isolated cases and in only in a minor fraction of normal tissue cells. Thus, the epigenetic profiles is considered to be a hallmark of cancer development initiation. PCR-based DNA fingerprinting method called methylation-sensitive amplified fragment length polymorphism (MS-AFLP) analysis enables simultaneous genome-wide detection of DNA hypermethylation and hypomethylation in tumor tissue. The array-based platform, which we adapted from former platform, interrogates over 9500 independent loci, corresponding to the NotI sites mapped throughout the human genome. We identified cancer related genes involved in WNT signaling, AXON guidance and Homeobox genes.
Free Research Field	消化器外科学
Academic Significance and Societal Importance of the Research Achievements	近年、網羅的ゲノム検索により多くの遺伝子が同定されました。大腸癌276症例のwhole genome studyによると腫瘍抑制遺伝子APC が関与するWNTシグナル伝達系において、その経路のどこかに遺伝子異常がある大腸癌の頻度は92-97%と非常に高い数値を示しました。すなわち、APCに異常を認めなくても、APCのシグナル伝達に関わる遺伝子の異常を多くの大腸癌が有していたという事です。この結果より、一連のシグナル伝達系に関わる遺伝子変化を包括的に検索し、解析する事の重要性が示されました。しかしながら、このような網羅的ゲノム検索を正常組織で行い、癌組織の変化と関連づけた報告はありません。