Next generation sequencing-based molecular detection of tumor-type specific fusion genes in bone and soft tissue tumors

• Project/Area Number: 15K08389
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: University of Occupational and Environmental Health, Japan
• Principal Investigator: HISAOKA Masanori 産業医科大学, 医学部, 教授 (40218706)
• Co-Investigator(Kenkyū-buntansha): 松山 篤二 産業医科大学, 大学病院, 講師 (80351021)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 骨軟部腫瘍 / 融合遺伝子 / 次世代シークエンス / RT-PCR / FISH / FFPE / 病理診断 / 滑膜肉腫 / ユーイング肉腫 / 粘液型脂肪肉腫 / 次世代シーケンス

Outline of Final Research Achievements

Our initial attempt to detect tumor type-specific fusion genes by next generation sequencing (NGS) was unsuccessful when we used ordinary formalin-fixed, paraffin-embedded (FFPE) bone and soft tissue tumors. The result suggested that FFPE tumor tissue is not suitable for such a state-of-the-art molecular analysis. We, therefore, subjected snap frozen tumor tissues to NGS, and could identify a few unique fusion genes (i.e. PAX3-MAMAL, etc) that had been unpredictable. Subsequent clinicopathologic and molecular analyses of accumulated tumor samples harboring the identical genetic alternations demonstrated some clinicopathologic diversities in such tumors. Thus, we believe that NGS is a potentially useful molecular technique as a diagnostic adjunct of bone and soft tissue tumors.

Research Products

• [Journal Article] Clinicopathologic diversity of undifferentiated sarcoma with BCOR-CCNB3 fusion: Analysis of 11 cases with a reappraisal of the utility of immunohistochemistry for BCOR and CCNB3. (2017)
  • Author(s): Matsuyama A, Shiba E, Umekita Y, Nosaka K, Kamio T, Yanai H, Miyasaka C, Watanabe R, Ito I, Tamaki T, Hayashi S, Hisaoka M.
  • Journal Title: American Journal of Surgical Pathology Volume: 41 Issue: 12 Pages: 1713-1721
  • DOI: 10.1097/pas.0000000000000934
  • Peer Reviewed
• [Journal Article] Protuberant fibro-osseous lesion of the skull: two cases with occipital lesions. (2017)
  • Author(s): Sato N, Aoki T, Mukai N, Yotsumoto S, Irie K, Hisaoka M.
  • Journal Title: Virchows Arch Volume: 470 Issue: 6 Pages: 717-720
  • DOI: 10.1007/s00428-017-2111-5
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 骨軟部腫瘍 (2017)
  • Author(s): 久岡正典
  • Journal Title: 臨床病理 Volume: 65 Pages: 1028-1037
• [Presentation] BCOR-CCNB3陽性未分化肉腫11例の臨床病理学的解析ならびにCCNB3ならびにBCOR免疫組織化学の診断学的有用性の再検討 (2017)
  • Author(s): 松山篤二、柴 瑛介、久岡正典
  • Organizer: 第63回日本病理学会 秋期特別総会
• [Presentation] Biphenotypic sinonasal sarcomas with PAX3-MAML3 fusion: report of 2 cases. (2017)
  • Author(s): Atsuji Matsuyama, Eisuke Shiba, Yukio Nakatani, Kazuyoshi Uchihashi, Masanori Hisaoka
  • Organizer: 第106回日本病理学会総会