New identification of genetic abnormalities associated with gastric carcinogenesis by comprehensive analysis of intestinal metaplasia

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K20836
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: Kyoto University
• Principal Investigator: Kumagai Ken 京都大学, 医学研究科, 客員研究員 (10912040)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: 胃癌 / 腸上皮化生 / 遺伝子解析

Outline of Final Research Achievements

We obtained metaplastic and non-metaplastic epithelium from gastric cancer cases with Helicobacter pylori infection. We used a gastric gland as a sample for DNA analysis and multiple glands as a sample for DNA and RNA analysis. We extracted DNA and RNA from each sample. DNA sequence and RNA expression level were analyzed using a next-generation sequencer, and copy number changes were calculated based on the obtained genomic data. We found that each metaplastic glands have a much higher number of genetic mutations than non-metaplastic glands. We also found that the gland of intestinal metaplasia clonally expands by repeating division. We also found that the expression of gene repair enzymes of metaplastic gland was lower than that of non-metaplastic glands even in the same cases.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

腸上皮化生腺管が同一個人においても非化生腺管と比較して遺伝子変異数が多く、遺伝子修復酵素の発現が低下していることがわかった。これはヘリコバクターピロリ菌が感染した個人の胃粘膜において、腸上皮化生が見られた場合は胃癌の発癌リスクであることを示唆し、胃癌の定期スクリーニングを行う必要性の高い集団の選別に役立つ。ひいては医療資源の効率的な配分に寄与する。