Analysis of the oncogenesis mechanism and the pathology of malignant mesothelioma based on BAP1 gene mutation

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K08731
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Hyogo Medical University
• Principal Investigator: Tsujimura Tohru 兵庫医科大学, 医学部, 教授 (20227408)
• Co-Investigator(Kenkyū-buntansha): 佐藤 鮎子 兵庫医科大学, 医学部, 講師 (20419823) ; 阿部 晋也 兵庫医科大学, 医学部, 助教 (70596725) ; 篠原 義康 兵庫医科大学, 医学部, 助教 (60723509)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 悪性中皮腫 / BAP1 / 細胞増殖 / 細胞遊走 / 予後

Outline of Final Research Achievements

Using the genome editing technique, p16-KO mesothelial cells, BAP1-KO mesothelial cells, and p16 & BAP1-DKO mesothelial cells were produced. In p16-KO mesothelial cells, no obvious change was observed in cell morphology, proliferative ability, and migratory ability, whereas in BAP1-KO mesothelial cells, the cells became larger and migratory ability, but not proliferative ability, was suppressed. By gene expression profile analysis, we found a cell migration factor X whose expression is markedly reduced in BAP1-KO mesothelial cells. BAP1 immunohistochemistry of epithelioid mesothelioma revealed that BAP1-positive cases had a poorer prognosis than BAP1-negative cases. BAP1 mutations are frequently found in epithelioid mesothelioma but appear to be less associated with malignancy.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

本研究成果により、BAP1変異は細胞増殖能よりも細胞遊走能に関与していることが明らかになり、それを担う候補分子として細胞遊走因子Xを見出している点に学術的意義がある。これらの知見は、BAP1変異を基軸とした悪性中皮腫の治療開発の重要性を支持するものであり、悪性中皮腫患者への福音になると期待される点に社会的意義がある。