Chromosomal translocation and the involvement of DNA repair system in sarcoma.
| Project/Area Number |
18K09110
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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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| Review Section |
Basic Section 56020:Orthopedics-related
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| Research Institution | Oita University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
織田 信弥 独立行政法人国立病院機構(九州がんセンター臨床研究センター), その他部局等, 腫瘍遺伝学研究室長 (40333372)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 肉腫 / 染色体転座 / 融合遺伝子 / DNA二本鎖切断修復 |
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| Outline of Final Research Achievements |
Disease-specific chromosomal translocation and the resulting fusion genes are thought to contribute to the carcinogenesis of sarcomas. Abnormalities in the DNA double-strand break repair system (homologous recombination, HR; non-homologous end-joining, NHEJ) are thought to be involved in the development of chromosomal translocations, but the details of the molecular mechanism are still unclear. In this study, we analyzed the expression and dysfunction of the factors responsible for HR and NHEJ in detail at the gene and protein expression levels and confirmed the activation of the HR pathway in various translocation-positive sarcoma cells.
Based on these achievements, we worked on the construction of a model system that can verify the in vitro chromosomal translocation in sarcoma cells.
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| Academic Significance and Societal Importance of the Research Achievements |
腫瘍における染色体転座はこれまでNHEJにより生起しているものと考えられてきたが、我々はむしろHR径路を介して生起しているのではないかと仮定し研究を進めて来た。その結果は、転座陽性肉腫細胞におけるHR径路の活性化を示唆している。HR径路を介した染色体転座は複数のDNA修復過程の異常を背景にしている可能性があるが、このようなDNA修復異常を正確にとらえ、転座の基礎となるDNA修復過程の全貌を明らかにするためには、各種DNA修復異常の意義を検証可能なモデル系を構築する必要がある。HRによる肉腫型染色体転座を再構成するin vitroモデル系を構築しようとする本研究は世界初の試みといえる。
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Report
(4 results)
Research Products
(26 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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[Journal Article] Clinical outcome of primary giant cell tumor of bone after curettage with or without perioperative denosumab in Japan: from a questionnaire for JCOG 1610 study2018
Author(s)
Urakawa H, Yonemoto T, Matsumoto S, Takagi T, Asanuma K, Watanuki M, Takemoto A, Naka N, Matsumoto Y, Kawai A, Kunisada T, Kubo T, Emori M, Hiraga H, Hatano H, Tsukushi S, Nishida Y, Akisue T, Morii T, Takahashi M, Nagano A, Yoshikawa H, Sato K, Kawano M, Hiraoka K, Tanaka K, Iwamoto Y, Ozaki T.
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Journal Title
World Journal of Surgical Oncology
Volume: 16
Issue: 1
Pages: 162-162
DOI
NAID
Related Report
Peer Reviewed
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[Presentation] Results of a randomized phase II/III study comparing perioperative adriamycin plus ifosfamide and gemcitabine plus docetaxel for high-grade soft tissue sarcomas: Japan Clinical Oncology Group study JCOG1306.2020
Author(s)
Tanaka K, Machida R, Kawai A, Nakayama R, Tsukushi S, Asanuma K, Matsumoto Y, Hiraga H, Hiraoka K, Watanuki M, Yonemoto T, Abe S, Katagiri H, Nishida Y, Nagano A, Suehara Y, Kataoka T, Fukuda H, Ozaki T, Iwamoto Y
Organizer
2020 Annual Meeting of American Society of Clinical Oncology
Related Report
Int'l Joint Research
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