2020 Fiscal Year Final Research Report
Establishment of a bio-assay for DNA homologous recombination ability using breast cancer cells to catalog responsible genetic alterations
| Project/Area Number |
18K19585
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 55:Surgery of the organs maintaining homeostasis and related fields
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| Research Institution | Nagasaki University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
中沢 由華 名古屋大学, 環境医学研究所, 助教 (00533902)
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| Project Period (FY) |
2018-06-29 – 2021-03-31
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| Keywords | 乳癌 / 相同組換え修復 |
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| Outline of Final Research Achievements |
We have established a system to measure the ability of DNA homologous recombination repair using primary breast cancer cells directly grown from breast cancer tissues. The system uses fluorescence immunostaining for EdU, CENP-F, and 53BP1 after olaparib treatment and scores by the number of DNA double-strand breaks in the G2 phase before and after 24 h treatment. This system was validated using siRNA-based BRCA1 knockdown cells.
Using the system, we selected five cases in which homologous recombination seemed to be impaired and performed whole genome sequencing. We did not identify any known mutations which have been suggested to be associated with hereditary beast cancers; however, we identified some alterations that fit the hereditary model. The functional analysis of these genes is necessary.
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| Free Research Field |
内分泌腫瘍学
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| Academic Significance and Societal Importance of the Research Achievements |
遺伝子変異解析では、病的意義が判明している既知の遺伝子変異を検出した場合のみDNA相同組み換え修復能欠損があるかどうか、ひいては特定の薬剤の適応となるかが分かるが、いまだ全ての変異が明らかにされているわけではない。しかし、実際に乳癌組織より細胞を培養し、本研究で開発した手法を用いれば、DNA相同組み換え修復能を予想でき、薬剤を選択できる可能性が示唆された。
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