Research on the tumorigenic mechanism of pediatric solid tumors by analyzing a epigenetics related gene

• Project/Area Number: 16K08745
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Keio University
• Principal Investigator: Okita Hajime 慶應義塾大学, 医学部(信濃町), 准教授 (50317260)
• Co-Investigator(Kenkyū-buntansha): 清河 信敬 国立研究開発法人国立成育医療研究センター, 小児血液・腫瘍研究部, 部長 (60195401)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: がん / 腎腫瘍 / 遺伝子発現 / 腫瘍 / 病理学

Outline of Final Research Achievements

Clear cell sarcoma of the kidney is a pediatric renal tumor and characterized by an intragenic duplication mutation of BCOR. The intragenic duplicated sequence of this gene showed no definite transformation ability in multiple cell lines, and transformation with this gene is likely to be dependent on the cellular context. However its overexpression in 293 cells changed gene expression, including several epigenetics related genes, and it was suggested that this gene might be involved in tumorigenesis.

Academic Significance and Societal Importance of the Research Achievements

BCOR遺伝子内重複変異による腫瘍発生の機序は今までほとんど明らかにされていない。発生機序の解析の積み重ねにより、診断法・治療法開発や、BCORの機能の解明につながることが期待される。

Research Products

• [Journal Article] Combined Genetic and Chromosomal Characterization of Wilms Tumors Identifies Chromosome 12 Gain as a Potential New Marker Predicting a Favorable Outcome (2019)
  • Author(s): Haruta Masayuki、Arai Yasuhito、Okita Hajime、Tanaka Yukichi、Takimoto Tetsuya、Sugino Ryuichi P.、Yamada Yasuhiro、Kamijo Takehiko、Oue Takaharu、Fukuzawa Masahiro、Koshinaga Tsugumichi、Kaneko Yasuhiko
  • Journal Title: Neoplasia Volume: 21 Issue: 1 Pages: 117-131
  • DOI: 10.1016/j.neo.2018.10.007
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 小児横紋筋肉腫の分子病理 (2018)
  • Author(s): 大喜多肇
  • Organizer: 第60回日本小児血液・がん学会学術集会
  • Invited
• [Presentation] Identification of BCOR internal tandem duplication in circulating tumor DNA from children with renal tumors. (2018)
  • Author(s): Ueno-Yokohata H, Okita H, Nakasato K, Hishiki T, Tsujimoto S, Shirai R, Osumi T, Yoshimura S, Yamada Y, Shioda Y, Kiyotani C, Terashima K, Miyazaki O, , Matsumoto K, Nobutaka Kiyokawa, Takako Yoshioka and Motohiro Kato
  • Organizer: International Society of Paediatric Oncology
  • Int'l Joint Research
• [Presentation] 腎芽腫において予後と相関する遺伝子・染色体異常 (2018)
  • Author(s): 1.春田 雅之, 新井 康仁, 大喜多 肇, 上條 岳彦, 野崎 美和子, 大植 孝治, 福澤 正洋, 越永 従道．
  • Organizer: 第77回日本癌学会学術総会
• [Presentation] 小児腎腫瘍におけるポリコーム複合体構成因子の発現解析 (2017)
  • Author(s): Ueno H. Okita H, Kiyokawa N.
  • Organizer: 第58回日本小児血液・がん学会学術集会