Elucidation of cancer development mechanism in which traces of driver genes disappear

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K19392
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 47:Pharmaceutical sciences and related fields
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: NIshina Hiroshi 東京医科歯科大学, 難治疾患研究所, 教授 (60212122)
• Project Period (FY): 2018-06-29 – 2020-03-31
• Keywords: がん遺伝子 / ドライバー遺伝子 / 肝がん / 肝細胞 / YAP

Outline of Final Research Achievements

Genes that cause cancer such as oncogenes and tumor suppressor genes are called driver genes. The mutation in the driver genes cause the cells to acquire proliferative capacity and lead to cancer formation. On the other hand, there are many cancers whose driver genes cannot be found. The purpose of this study was "to elucidate the mechanism of cancer development in which traces of driver genes disappear." The gene encoding the active transcriptional cofactor YAP was transiently introduced into mouse livers. As a result, liver cancer developed after 3 months. Interestingly, no expression of causative activated YAP was observed in the liver cancers. Thus, this experimental system was considered to be "onset of cancer in which traces of the driver gene disappear."

Free Research Field

分子細胞生物学

Academic Significance and Societal Importance of the Research Achievements

がんゲノム解析の結果、ドライバー遺伝子変異が検出されないがんも存在することが報告されるが、その原因を探求している研究はほとんど無い。それ故、本研究は国内外を通じて、ユニークな研究であると考えられる。また、申請者は、マウスを用いた肝がん発症機構の研究にモザイク解析法を導入したこと、正常肝細胞がゲノム変異無しでがん化する可能性を見出したこともユニークな研究になっていると考えられる。本分子機構の解明は、初期段階の発がんにおける微小環境の役割解明に繋がると期待される。初期段階のがん発症の分子機構が解明されれば、がん予防を目指す先制医療の基盤的知見となる。