Oncogenic role of aberrant SWI/SNF chromatin remodeling complex in synovial sarcoma
| Project/Area Number |
17K10985
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Keio University |
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Principal Investigator |
Nakayama Robert 慶應義塾大学, 医学部(信濃町), 講師 (00365298)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 発がん / 遺伝子 / ゲノム / トランスレーショナル・リサーチ / 融合遺伝子 / SWI/SNF複合体 / 肉腫 / 滑膜肉腫 / 希少がん / AYA世代 / SWI/SNF / BAF / クロマチンリモデリング複合体 / SS18-SSX / 遺伝子発現制御 / 悪性軟部腫瘍 / 癌 / トランスレーショナルリサーチ |
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| Outline of Final Research Achievements |
Synovial sarcoma is one of the common malignant soft tissue sarcomas in adolescent and young adult patients. Nearly 100% of tumors contain the pathognomonic t(X;18)(p11.2;q11.2) chromosomal translocation that produces the hallmark SS18-SSX fusion protein. Given that SS18 is a dedicated subunit of SWI/SNF chromatin remodeling complexes, we hypothesized that malfunction of the aberrant SWI/SNF complexes that contain the SS18-SSX fusion should be responsible for the development of synovial sarcoma, and conducted biochemical analyses by knocking down the SS18-SSX gene in synovial sarcoma cell lines. Our study demonstrated that SS18-SSX globally hijacked BAF complexes on chromatin to activate a transcriptional signature specific to synovial sarcoma.
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| Academic Significance and Societal Importance of the Research Achievements |
滑膜肉腫は思春期から若年成人に発生する代表的な悪性軟部腫瘍である。進行例に対する有効な治療法がないため、疾患特異的融合遺伝子SS18-SSXによる発がん機構を標的とした新規治療の開発に期待が高まっており、SS18-SSXの機能解析をおこなった本研究の成果はそれに向けた新規知見を提供した。さらに、本研究の成果は、SWI/SNF複合体の異常によって生じる様々な疾患における病態解明のモデルを提供した、という点で、非常に重要である。
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Report
(4 results)
Research Products
(15 results)
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[Journal Article] Prospective comparison of various radiological response criteria and pathological response to preoperative chemotherapy and survival in operable high-grade soft tissue sarcomas in the Japan Clinical Oncology Group study JCOG03042018
Author(s)
Tanaka K, Ogawa G, Mizusawa J, Naka N, Kawai A, Takahashi M, Hiruma T, Matsumoto Y, Tsuchiya H, Nakayama R, Hatano H, Emori M, Hosaka M, Yoshida Y, Toguchida J, Abe S, Asanuma K, Yokoyama R, Hiraga H, Yonemoto T, Morii T, Matsumoto S, Nagano A, Yoshikawa H, Fukuda H, Ozaki T, Iwamoto Y.
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Journal Title
World Journal of Surgical Oncology
Volume: 16
Issue: 1
Pages: 160-160
DOI
Related Report
Peer Reviewed
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