NF2 genetic alterations in diagnosis of malignant mesothelioma

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07425
• 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: Sato Ayuko 兵庫医科大学, 医学部, 講師 (20419823)
• Co-Investigator(Kenkyū-buntansha): 辻村 亨 兵庫医科大学, 医学部, 教授 (20227408) ; 結城 美智子 兵庫医科大学, 医学部, 助教 (60467587) ; 篠原 義康 兵庫医科大学, 医学部, 助教 (60723509)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 悪性中皮腫 / NF2

Outline of Final Research Achievements

The NF2 gene is often altered in malignant mesothelioma. The utility of immunostaining against Merlin, a protein coded by the NF2 gene, in pathological diagnosis was investigated. By using mesothelioma cell lines with the mutated NF2 gene, we found an immunohistochemical method in which Merlin immunostaining properties were concordant with the mutation status of the NF2 gene. In cultured mesothelioma cells and clinical specimens obtained from tumor tissues or pleural effusions of Japanese patients with malignant pleural mesothelioma, Merlin immunostaining properties were correlated with the mutation status of the NF2 gene identified by whole exome sequencing or NF2 FISH analysis. These results suggested that Merlin immunostaining is a useful screening method to investigate the inactivation of NF2/Merlin in malignant mesothelioma.

Free Research Field

病理学

Academic Significance and Societal Importance of the Research Achievements

異型中皮細胞の良悪性の判定においては、悪性中皮腫に特徴的ながん抑制遺伝子の異常の検出が有用であり、CDKN2AおよびBAP1遺伝子の異常については日常の病理診断に取り入れられるようになってきたが、NF2遺伝子についてはほとんど解析されてこなかった。本研究成果により、NF2遺伝子異常の有無を予測する簡便な手法としてMerlin免疫染色の有用性が示されたことより、NF2/Merlin不活化が発症に関与する中皮腫を見出し、適切な治療法の選択に繋がることが期待される。