2018 Fiscal Year Final Research Report
Cross-organ analysis of DNA methylation alteration during multi-organ carcinogenesis
Project/Area Number |
16K08720
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Experimental pathology
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Research Institution | Keio University |
Principal Investigator |
Arai Eri 慶應義塾大学, 医学部(信濃町), 専任講師 (40446547)
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Research Collaborator |
KANAI Yae
OHARA Kentaro
GOTOH Masahiro
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Keywords | DNAメチル化 / 発がん / 臓器共通性 / 胃がん / 臓器特異性 |
Outline of Final Research Achievements |
Genes encoding transcription factors involved in development and differentiation are commonly methylated in multiple organ cancers. Disruption of the differentiated state may be a common feature of DNA methylation alterations during carcinogenesis. Gastric carcinoma-specific DNA hypermethylation was identified based on methylome analysis of multiple organs. Our criteria may be useful for detecting the primary organ in cases of cancer of unknown primary site. Specific DNA hypermethylation was not observed only in gastric carcinoma but also in noncancerous gastric tissue. Specific DNA hypermethylation may not occur cancer-specific but organ-specific, and not be a functional event but a surrogate marker for gastric tissue.
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Free Research Field |
分子病理学、疾患エピゲノム
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Academic Significance and Societal Importance of the Research Achievements |
これまで臓器毎に報告されてきたがんのDNAメチル化異常について、臓器横断的に解析することにより臓器共通性と臓器特異性を見出したことが本研究の独創性と重要性である。一般的にがんでは、細胞の分化に関わる遺伝子のDNAメチル化に異常があり、分化状態が不安定になることが細胞ががんになる際の特徴であると考えられた。DNAメチル化はヒトの発生過程で臓器・細胞特異的に形成されることに着目し、原発不明がんの原発臓器診断において有用な臓器特異的マーカーのない胃がんの臓器特異的DNAメチル化診断指標を同定した。
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