Epigenetic analysis for a novel therapeutic target in esophagogastric junction adenocarcinoma
| 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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Report
(3 results)
Research Products
(11 results)
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[Journal Article] Recent incidence trend of surgically resected esophagogastric junction adenocarcinoma and microsatellite instability status in Japanese patients.2018
Author(s)
Imamura Y, Watanabe M, Toihata T, Takamatsu M, Kawachi H, Haraguchi I, Ogata Y, Yoshida N, Saeki H, Oki E, Taguchi K, Yamamoto M, Morita M, Mine S, Hiki N, Baba H, Sano T.
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Journal Title
Digestion.
Volume: 99
Issue: 1
Pages: 6-13
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] MSI-L tumors exhibited an intermediate tumor immune microenvironment between MSI-H and MSS in esophagogastric junction adenocarcinoma.2019
Author(s)
Imamura Y, Toihata T, Takamatsu M, Tanaka N, Mine S, Mori S, Oki E, Morita M, Baba H, Sano T, Watanabe M
Organizer
11th AACR-JCA Joint Conference
Related Report
Int'l Joint Research
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