2020 Fiscal Year Final Research Report
Generation and characterization of BCOR-ITD tumor models
| Project/Area Number |
18K07057
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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 49030:Experimental pathology-related
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| Research Institution | National Center for Child Health and Development |
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Principal Investigator |
Ueno Hitomi 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, 研究員 (30435630)
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| Co-Investigator(Kenkyū-buntansha) |
高田 修治 国立研究開発法人国立成育医療研究センター, システム発生・再生医学研究部, 部長 (20382856)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | 小児腫瘍 / BCOR / ゲノム編集 |
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| Outline of Final Research Achievements |
To elucidate how BCOR internal tandem duplication (BCOR-ITD) causes tumorigenesis, we attempted to generate model mice and model cells with Bcor-ITD. In this study, we applied genome editing in fertilized eggs, which resulted in unintended mutations in some cells, making it difficult to create a line of Bcor-ITD mice. However, we succeeded in establishing Bcor-ITD positive ES cells and fibroblasts from heterozygote mice.
The Bcor-ITD-expressing fibroblast cell line showed an upward trend in the expression of Bcor compared to the wild-type expressing line. In fibroblasts, when the activated X chromosome was Bcor-ITD, the gene expression of Bcor tended to increase than that of the wild type. This result is consistent with the over expression of BCOR-ITD in clear cell sarcoma of the kidney, suggests that mutation acquisition may result in regulated BCOR gene expression.
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| Free Research Field |
小児腫瘍
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| Academic Significance and Societal Importance of the Research Achievements |
変異モデルは、様々な遺伝子変異の機能解析や治療薬開発に必須である。
本研究では小児固形腫瘍で発見したBCOR変異（BCOR-ITD）を有するマウスモデル細胞を作出し、その分子生物学的解析から腫瘍で認める特徴の一部が、変異獲得により生じていると推測できる結果を得た。また変異を有するES細胞を樹立したことにより、今後、BCOR-ITDによる異常な細胞分化や腫瘍化の観察について可能性が広がった。本研究の成果は、BCOR-ITD陽性腫瘍の解明に向けた足掛かりになったと考える。
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