| Project/Area Number |
17K19619
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Tumor biology and related fields
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| Research Institution | Japanese Foundation for Cancer Research |
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Principal Investigator |
Imamura Yu 公益財団法人がん研究会, 有明病院 消化器外科, 副医長 (70583045)
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| Co-Investigator(Kenkyū-buntansha) |
渡邊 雅之 公益財団法人がん研究会, 有明病院 消化器外科, 部長 (80254639)
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| Project Period (FY) |
2017-06-30 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2018: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2017: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| Keywords | 食道胃接合部腺癌 / メチル化 / LINE-1 / エピジェネティクス / メチル化異常 |
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| Outline of Final Research Achievements |
Upper-gastrointestinal adenocarcinoma can be classified into 4 distinct molecular subtypes by NGS, like chromosomal instability（CIN）, genetically stable（GS）, Epstein-Barr related type (EBV), and microsatellite instable-high (MSI-H). However, this subtyping is too much complicated, and not easy to be applied for clinical practice, especially in dividing CIN and GS. This study revealed the patient with LINE-1 hypomethylated tumor (LINE-1≦59.0) was significantly associated with TP53 mutation, Ki-67 index, and worst clinical outcome in 4-yr follow up. Our data suggest that LINE-1 hypomethylated tumor (LINE-1≦59.0) may be adistinct tumor phenotype, and LINE-1 methylation level can be a useful marker in non-EBV/non-MSI-H EGJ adenocarcinoma.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究によってNon-EBV, non-MSI-Hの食道胃接合部腺癌において、LINE-1のメチル化レベル59以下を示す一群はTP53変異率が高く、細胞周期が更新しており、予後不良の特徴的一群であると言うことが判明した。これまでの次世代シーケンサーを用いたmolecular subtype 分類では、CINとGSの分類は実臨床には不向きであり、その点でLINE-1メチル化レベルは、より安価・簡便で臨床的に有用な予後マーカーとなることが判明した。
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