Identification of novel fusion gene in inflammatory myofibroblastic tumor

• Project/Area Number: 16K08669
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Kyushu University
• Principal Investigator: YAMAMOTO HIDETAKA 九州大学, 大学病院, 准教授 (30404073)
• Research Collaborator: Nosaki Yui
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 炎症性筋線維芽細胞腫瘍 / 融合遺伝子 / ALK / ROS1 / NTRK3 / 免疫組織化学染色 / 病理 / 診断 / 病理学

Outline of Final Research Achievements

We discovered ALK, ROS1 and NTRK3 gene fusions in approximately 60, 5 and 5% of inflammatory myofibroblastic tumor (IMT), respectively. In rare cases, immunohistochemical staining (IHC) with ALK1 antibody was negative but IHC with 5A4 antibody was positive, suggesting that ALK1 can cause false negative result of ALK expression. IMT with ETV6-NTRK3 gene fusion showed nuclear and cytoplasmic immunoreactivity for pan-Trk, suggesting a diagnostic utility of this antibody.

Academic Significance and Societal Importance of the Research Achievements

IMTは炎症性病変と病理組織像が類似しているため鑑別診断がしばしば困難である。ALK, ROS1, NTRK3融合遺伝子の検出は診断的価値が高く、IMTの確定診断の精度を高めることが期待される。またALK, RO1, NTRK3 (pan-Trk)に対する免疫染色は、その融合遺伝子陽性例の簡便なスクリーニングとして有用であり、分子標的治療の対象となりうる患者の選択に役立つ可能性がある。

Research Products

• [Journal Article] ALK, ROS1 and NTRK3 gene rearrangements in inflammatory myofibroblastic tumors. (2016)
  • Author(s): Yamamoto H, Yoshida A, Taguchi K, Kohashi K, Hatanaka Y, Yamashita A, Mori D, Oda Y
  • Journal Title: Histopathology Volume: 69(1) Issue: 1 Pages: 72-83
  • DOI: 10.1111/his.12910
  • Peer Reviewed
• [Presentation] Diagnostic utility of pan-TRK immunohistochemistry in inflammatory myofibroblastic tumor (2019)
  • Author(s): Yamamoto H, Nozaki Y, Kohashi K, Oda Y.
  • Organizer: The 108th Annual Meeting of the United States and Canadian Academy of Pathology
  • Int'l Joint Research
• [Presentation] 炎症性筋線維芽細胞腫瘍におけるpan-TRK免疫組織化学染色の診断的有用性 (2019)
  • Author(s): 山元英崇、野崎優衣、孝橋賢一、田口健一、小田義直
  • Organizer: 第108回日本病理学会総会
• [Presentation] 甲状腺乳頭癌におけるROS1発現とROS1遺伝子再構成の頻度及び臨床病理学的解析 (2018)
  • Author(s): 畑中優衣、山元英崇、岩崎健、佐藤方宣、次郎丸梨那、小田義直
  • Organizer: 第107回日本病理学会総会