Comprehensive understanding of genomic abnormalities and clinicopathological characteristics of early mesothelioma: Elucidation of oncogenesis and pathogenesis of mesothelioma

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07419
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49020:Human pathology-related
• 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) ; 篠原 義康 兵庫医科大学, 医学部, 助教 (60723509) ; 結城 美智子 兵庫医科大学, 医学部, 助教 (60467587)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 早期中皮腫 / ゲノム異常

Outline of Final Research Achievements

Early mesothelioma arises from BAP1 mutation, CDKN2A homozygous deletion, and genomic abnormalities other than BAP1 and CDKN2A. By gene expression profile analysis of BAP1-KO mesothelial cells, an anoikis resistance inducing factor X, whose expression is enhanced in BAP1-KO mesothelial cells, was found. Mesothelial cells possessing BAP1 mutation may be regulated to prevent apoptosis even if they float in pleural effusion. Whole-exome sequencing analysis of invasive mesothelioma specimens 5 years after the first medical examination of a patient with preinvasive mesothelioma possessing BAP1 loss revealed mutations in the MAGI2 gene, which is involved in the cell cycle, in addition to the BAP1 gene. MAGI2 may be involved in the progression of preinvasive mesothelioma to invasive mesothelioma.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

早期中皮腫の発生には複数の発がん機構があることが示された。BAP1変異は中皮細胞にアノイキス耐性を誘導している可能性があり、それを担う候補分子としてアノイキス耐性誘導因子Xを見出している点に学術的意義がある。前浸潤性中皮腫から浸潤性中皮腫への進展に関与する候補分子は、中皮腫の治療開発に繋がる可能性があり、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。