Investigation of draggable fusion genes and diagnostic biomarker in bone and soft tissue sarcoma

• Project/Area Number: 18K09112
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Sapporo Medical University
• Principal Investigator: Hamada Shuto 札幌医科大学, 医学部, 研究員 (90813626)
• Co-Investigator(Kenkyū-buntansha): 江森 誠人 札幌医科大学, 医学部, 講師 (20580286) ; 塚原 智英 札幌医科大学, 医学部, 准教授 (20404634)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2020: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 骨軟部腫瘍 / 融合遺伝子 / 類上皮肉腫 / 肉腫 / 軟部肉腫 / バイオマーカー / 転移

Outline of Final Research Achievements

Fusion genes have been reported to occur in several bone and soft tissue sarcomas (BSTT). We tried to detect new draggable fusion genes to improve overall survival in BSTT. Especially, we analyzed fusion genes of epithelioid sarcoma. We identified nine candidates of fusion genes in a tumor sample of a 15 year-old Japanese patient, using next-generation sequences. Of them, GATSL2×GTF2I was confirmed to be a fusion.

Academic Significance and Societal Importance of the Research Achievements

類上皮肉腫は今でも予後が改善されていない予後不良な肉腫の1つである。類上皮肉腫では腫瘍特異的な融合遺伝子は同定されておらず、我々はこの融合遺伝子の同定し、それを標的とした治療法を開発することで、予後改善のための研究基盤を確立する。次世代シークエンサーを用いた解析によって、1つの融合遺伝子候補を同定した。現在治療の標的になる融合遺伝子かの解析を行っている。

Research Products

• [Journal Article] Do We Have Adequate Flexion-extension Radiographs for Evaluating Instability in Patients With Lumbar Spondylolisthesis? (2020)
  • Author(s): Morita Tomonori、Yoshimoto Mitsunori、Terashima Yoshinori、Tanimoto Katsumasa、Iesato Noriyuki、Ogon Izaya、Oshigiri Tsutomu、Teramoto Atsushi、Emori Makoto、Takashima Hiroyuki、Hirota Ryosuke、Fujimoto Shutaro、Yamashita Toshihiko
  • Journal Title: SPINE Volume: 45 Issue: 1 Pages: 48-54
  • DOI: 10.1097/brs.0000000000003203
• [Journal Article] Osteosarcoma in patients over 50 years of age: Multi-institutional retrospective analysis of 104 patients (2020)
  • Author(s): Nagano Akihito、Tanaka Kazuhiro、et al.
  • Journal Title: Journal of Orthopaedic Science Volume: 25 Issue: 2 Pages: 319-323
  • DOI: 10.1016/j.jos.2019.04.008
  • Peer Reviewed / Open Access
• [Journal Article] Prognosis of Primary Osteosarcoma in Elderly Patients: A Comparison between Young and Elderly Patients (2019)
  • Author(s): Tsuchie Hiroyuki、Emori Makoto、Nagasawa Hiroyuki、Miyakoshi Naohisa、Murahashi Yasutaka、Shimizu Junya、Mizushima Emi、Yamashita Toshihiko、Shimada Yoichi
  • Journal Title: Medical Principles and Practice Volume: 28 Issue: 5 Pages: 425-431
  • DOI: 10.1159/000500404
  • Peer Reviewed
• [Journal Article] Prognostic Impact of CD44 Expression in Patients With Myxofibrosarcoma (2019)
  • Author(s): TSUCHIE HIROYUKI、EMORI MAKOTO、MIYAKOSHI NAOHISA、NAGASAWA HIROYUKI、OKADA KYOJI、NANJYO HIROSHI、MURAHASHI YASUTAKA、MIZUSHIMA EMI、SHIMIZU JUNYA、YAMASHITA TOSHIHIKO、SHIMADA YOICHI
  • Journal Title: In Vivo Volume: 33 Issue: 6 Pages: 2095-2102
  • DOI: 10.21873/invivo.11709
• [Journal Article] Early Lymph Node Metastasis May Predict Poor Prognosis in Soft Tissue Sarcoma (2019)
  • Author(s): Emori Makoto、Tsuchie Hiroyuki、Nagasawa Hiroyuki、Sonoda Tomoko、Tsukamoto Arihiko、Shimizu Junya、Murahashi Yasutaka、Mizushima Emi、Takada Kohichi、Murase Kazuyuki、Iesato Kotoe、Igarashi Keita、Hori Tsukasa、Yamamoto Masaki、Sugita Shintaro、Miyakoshi Naohisa、Hasegawa Tadashi、Shimada Yoichi、Yamashita Toshihiko
  • Journal Title: International Journal of Surgical Oncology Volume: 2019 Pages: 1-5
  • DOI: 10.1155/2019/6708474
  • Peer Reviewed / Open Access
• [Journal Article] Treatment outcome of chest wall soft tissue sarcomas: Analysis of prognostic factors (2019)
  • Author(s): Nakahashi Naoya、Emori Makoto、Tsuchie Hiroyuki、Nagasawa Hiroyuki、Sonoda Tomoko、Takada Kohichi、Miyajima Masahiro、Watanabe Atsushi、Shimada Yoichi、Yamashita Toshihiko
  • Journal Title: Journal of Surgical Oncology Volume: 120 Issue: 7 Pages: 1235-1240
  • DOI: 10.1002/jso.25708
  • Peer Reviewed
• [Journal Article] Ten-year follow-up results of perioperative chemotherapy with doxorubicin and ifosfamide for high-grade soft-tissue sarcoma of the extremities: Japan Clinical Oncology Group study JCOG0304 (2019)
  • Author(s): Tanaka Kazuhiro、Mizusawa Junki、Naka Norifumi、Kawai Akira、et al.
  • Journal Title: BMC Cancer Volume: 19 Issue: 1 Pages: 1-7
  • DOI: 10.1186/s12885-019-6114-2
  • Peer Reviewed / Open Access
• [Journal Article] Impact of Acridine Orange in Patients With Soft Tissue Sarcoma Treated With Marginal Resection (2019)
  • Author(s): TSUCHIE HIROYUKI、EMORI MAKOTO、MIYAKOSHI NAOHISA、NAGASAWA HIROYUKI、OKADA KYOJI、MURAHASHI YASUTAKA、MIZUSHIMA EMI、SHIMIZU JUNYA、YAMASHITA TOSHIHIKO、SHIMADA YOICHI
  • Journal Title: Anticancer Research Volume: 39 Issue: 11 Pages: 6365-6372
  • DOI: 10.21873/anticanres.13849
  • Peer Reviewed
• [Journal Article] Combination of eribulin plus AKT inhibitor evokes synergistic cytotoxicity in soft tissue sarcoma cells (2019)
  • Author(s): Hayasaka Naotaka、Takada Kohichi、Nakamura Hajime、Arihara Yohei、Kawano Yutaka、Osuga Takahiro、Murase Kazuyuki、Kikuchi Shohei、Iyama Satoshi、Emori Makoto、Sugita Shintaro、Hasegawa Tadashi、Takasawa Akira、Miyanishi Koji、Kobune Masayoshi、Kato Junji
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 5759-5759
  • DOI: 10.1038/s41598-019-42300-z
  • Peer Reviewed / Open Access
• [Journal Article] Identification of Coiled-Coil Domain-Containing Protein 180 and Leucine-Rich Repeat-Containing Protein 4 as Potential Immunohistochemical Markers for Liposarcoma Based on Proteomic Analysis Using Formalin-Fixed, Paraffin-Embedded Tissue. (2019)
  • Author(s): Aoyama T, Takasawa A, Takasawa K, Ono Y, Emori M, Murata M, Hayasaka T, Fujitani N, Osanai M, Yamashita T, Hasegawa T, Sawada N.
  • Journal Title: Am J Pathol. Volume: in press Issue: 5 Pages: 1015-1028
  • DOI: 10.1016/j.ajpath.2019.01.013
  • Peer Reviewed
• [Presentation] 骨肉腫に対する養子免疫療法を目指したPBF TCRレトロウイルス産生細胞の樹立 (2019)
  • Author(s): 濱田修人, 塚原智英, 江森誠人, 久保輝文, 金関貴幸, 廣橋良彦, 山下敏彦, 鳥越俊彦.
  • Organizer: 34回日本整形外科学会基礎学術集会