Genetic characterization of unclassifiable small round cell sarcomas

• Project/Area Number: 15K19065
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Human pathology
• Research Institution: National Cancer Center Japan
• Principal Investigator: YOSHIDA AKIHIKO 国立研究開発法人国立がん研究センター, 中央病院, 医員 (80574780)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 肉腫 / 分類 / 遺伝子変異 / 融合遺伝子 / 病理診断 / 小円形細胞肉腫 / バイオマーカー / 免疫組織化学 / RNAシーケンス / 疾病分類

Outline of Final Research Achievements

Small round cell sarcoma is a diagnostic category that encompasses a variety of sarcoma entities which share predominantly small round-shaped tumor cytology. Most small round cell sarcomas are readily classifiable; however, approximately 5-10% of tumors defy definitive classification based on the present nosologic scheme. These unclassifiable small round cell sarcomas are hypothesized to consist of multiple distinct entities, each of which should be recognized and treated by specific strategy. In this study, we first identified a number of unclassifiable small round cell sarcomas in our archive, and then analyzed them by using clinicopathological and molecular methods including next generation sequencing. We identified a relatively large series of novel entities such as CIC-rearranged sarcoma and SMARCA4-deficient thoracic sarcoma, and characterized them in detail to better understand these under-recognized malignancies.

Research Products

• [Int'l Joint Research] Instituto Valenciano de Oncologia(Spain)
• [Journal Article] Minute Mesenchymal Chondrosarcoma within Osteochondroma: An Unexpected Diagnosis Confirmed by HEY1-NCOA2 Fusion (2018)
  • Author(s): Toki Shunichi、Motoi Toru、Miyake Mototaka、Kobayashi Eisuke、Kawai Akira、Yoshida Akihiko
  • Journal Title: Human Pathology Volume: Epub ahead of print Pages: 255-260
  • DOI: 10.1016/j.humpath.2018.03.014
  • Peer Reviewed / Open Access
• [Journal Article] INSM1 expression and its diagnostic significance in extraskeletal myxoid chondrosarcoma. (2018)
  • Author(s): Yoshida A, Makise N, Wakai S, Kawai A, Hiraoka N.
  • Journal Title: Mod Pathol. Volume: 印刷中 Issue: 5 Pages: 744-752
  • DOI: 10.1038/modpathol.2017.189
  • Peer Reviewed / Open Access
• [Journal Article] Review with novel markers facilitates precise categorization of 41 cases of diagnostically challenging, "undifferentiated small round cell tumors". A clinicopathologic, immunophenotypic and molecular analysis. (2017)
  • Author(s): Machado I, Yoshida A, Morales MGN, Abrahao-Machado LF, Navarro S, Cruz J, Lavernia J, Parafioriti A, Picci P, Llombart-Bosch A.
  • Journal Title: Ann Diagn Pathol. Volume: 34 Pages: 1-12
  • DOI: 10.1016/j.anndiagpath.2017.11.011
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Immunohistochemical analysis of NKX2.2, ETV4, and BCOR in a large series of genetically confirmed Ewing sarcoma family of tumors. (2017)
  • Author(s): Machado I, Yoshida A, Lopez-Guerrero JA, Nieto MG, Navarro S, Picci P, Llombart-Bosch A.
  • Journal Title: Pathol Res Pract. Volume: 213 Issue: 9 Pages: 1048-1053
  • DOI: 10.1016/j.prp.2017.08.002
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] CIC Break-Apart Fluorescence In Situ Hybridization Misses a Subset of CIC-DUX4 Sarcomas: A Clinicopathological and Molecular Study (2017)
  • Author(s): Yoshida A, Arai Y, Kobayashi E, Yonemori K, Ogura K, Hama N, Mukai W, Motoi T, Kawai A, Shibata T, N Hiraoka
  • Journal Title: Histopathology Volume: 印刷中 Issue: 3 Pages: 461-469
  • DOI: 10.1111/his.13252
  • Peer Reviewed
• [Journal Article] Clinicopathological and molecular characterization of SMARCA4-deficient thoracic (2017)
  • Author(s): Yoshida A, Kobayashi E, Kubo T, Kodaira M, Motoi T, Motoi N, Yonemori K, Ohe
  • Journal Title: Modern Pathology Volume: 印刷中 Issue: 6 Pages: 797-809
  • DOI: 10.1038/modpathol.2017.11
  • Peer Reviewed
• [Journal Article] CIC-rearranged Sarcomas: A Study of 20 Cases and Comparisons With Ewing Sarcomas (2016)
  • Author(s): Yoshida A, Goto K, Kodaira M, Kobayashi E, Kawamoto H, Mori T, Yoshimoto S, Endo O, Kodama N, Kushima R, Hiraoka N, Motoi T, Kawai A.
  • Journal Title: Am J Surg Pathol. Volume: 40 Issue: 3 Pages: 313-23
  • DOI: 10.1097/pas.0000000000000570
  • Peer Reviewed
• [Presentation] SMARCA4欠損型胸部肉腫12例の臨床病理学的・遺伝子的解析 (2017)
  • Author(s): 吉田朗彦、小林英介、久保崇、元井亨、元井紀子、川井章、河野隆志、岸本宏志、市川仁、平岡伸介
  • Organizer: 第106回日本病理学会総会
  • Place of Presentation: 京王プラザホテル（東京都、新宿区）
  • Year and Date: 2017-04-29
• [Presentation] Clinicopathological and Molecular Characterization of SMARCA4-Deficient Thoracic Sarcomas with Comparisons to Potentially Related Disease Entities (2017)
  • Author(s): Akihiko Yoshida, Eisuke Kobayashi, Takashi Kubo, Toru Motoi, Noriko Motoi, Akira Kawai, Takashi Kohno, Hiroshi Kishimoto, Hitoshi Ichikawa, Nobuyoshi Hiraoka
  • Organizer: United States & Canadian Academy of Pathology’s 106th Annual Meeting
  • Place of Presentation: San Antonio, TX, USA
  • Year and Date: 2017-03-07
  • Int'l Joint Research