Epigenetic analysis for a novel therapeutic target in esophagogastric junction adenocarcinoma

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K19619
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology and related fields
• Research Institution: Japanese Foundation for Cancer Research
• 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)
• 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)
• Project Period (FY): 2017-06-30 – 2019-03-31
• Keywords: 食道胃接合部腺癌 / メチル化 / LINE-1

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.

Free Research Field

消化器癌

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。