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 |
Review Section |
Medium-sized Section 55:Surgery of the organs maintaining homeostasis and related fields
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Research Institution | Nagasaki University |
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)
|
Project Period (FY) |
2018-06-29 – 2021-03-31
|
Project Status |
Completed (Fiscal Year 2020)
|
Budget Amount *help |
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2018: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
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Keywords | 乳癌 / 相同組換え修復 / 相同組み換え修復 / DNA修復 |
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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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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Report
(4 results)
Research Products
(20 results)
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[Journal Article] Digenic mutations in ALDH2 and ADH5 impair formaldehyde clearance and cause a multisystem disorder, AMeD syndrome2020
Author(s)
Oka Y, Hamada M, Nakazawa Y, ..., Tanaka M, Suganami T, Nakada S, Mitsutake N, Hara Y, Kato K, ..., Kaneko H, Matsumoto N, Matsuda F, Matsuo K, Takahashi Y, Mashimo T, Kojima S, Ogi T
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Journal Title
Science Advances
Volume: 6
Issue: 51
Pages: 7197-7197
DOI
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Peer Reviewed / Open Access
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[Journal Article] Topoisomerase I-driven repair of UV-induced damage in NER-deficient cells2020
Author(s)
Saha Liton Kumar、Wakasugi Mitsuo、Akter Salma、Prasad Rajendra、Wilson Samuel H.、Shimizu Naoto、Sasanuma Hiroyuki、Huang Shar-yin Naomi、Agama Keli、Pommier Yves、Matsunaga Tsukasa、Hirota Kouji、Iwai Shigenori、Nakazawa Yuka、Ogi Tomoo、Takeda Shunichi
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Journal Title
Proceedings of the National Academy of Sciences
Volume: 117
Issue: 25
Pages: 14412-14420
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Biallelic VPS35L pathogenic variants cause 3C/Ritscher-Schinzel-like syndrome through dysfunction of retriever complex.2020
Author(s)
Kato K, Okuno Y, Vasilev FF, Otomo T, Oishi H, Muramatsu H, Kawano Y, Oka Y, Nakazawa Y, Ogi T, Takahashi Y, Saitoh S.
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Journal Title
Journal of Medical genetics
Volume: 57
Issue: 4
Pages: 245-253
DOI
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Peer Reviewed / Int'l Joint Research
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[Journal Article] Papillary thyroid carcinoma in Ukraine after Chernobyl and in Japan after Fukushima: different histopathological scenarios.2020
Author(s)
Bogdanova TI, Saenko VA, Hashimoto Y, Hirokawa M, Zurnadzhy LY, Hayashi T, Ito M, Iwadate M, Mitsutake N, Rogounovitch T, Sakamoto A, Naganuma H, Miyauchi A, Tronko MD, Thomas G, Yamashita S, Suzuki S:
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Journal Title
Thyroid
Volume: 308
Issue: 9
Pages: 1-13
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] The Clinicopathological Results of Thyroid Cancer With BRAFV600E Mutation in the Young Population of Fukushima.2020
Author(s)
Iwadate M, Mitsutake N, Matsuse M, Fukushima T, Suzuki S, Matsumoto Y, Ookouchi C, Mizunuma H, Nakamura I, Nakano K, Sakamoto A, Hirokawa M, Ito M, Naganuma H, Hashimoto Y, Shimura H, Yamashita S, Suzuki S
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Journal Title
J Clin Endocrinol Metab
Volume: 105
Issue: 12
Pages: 573-573
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Ubiquitination of DNA Damage-Stalled RNAPII Promotes Transcription-Coupled Repair2020
Author(s)
Nakazawa Y, Hara Y, Oka Y, Komine O, van den Heuvel D, Guo C, Daigaku Y, Isono M, He Y, Shimada M, Kato K, Jia N, Hashimoto S, Kotani Y, Miyoshi Y, Tanaka M, Sobue A, Mitsutake N, Suganami T, Masuda A, Ohno K, Nakada S, Mashimo T, Yamanaka K, Luijsterburg MS, Ogi T
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Journal Title
Cell
Volume: 19
Issue: 6
Pages: 1228-1244
DOI
NAID
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Functional and clinical relevance of novel mutations in a large cohort of patients with Cockayne syndrome.2018
Author(s)
Calmels N, Botta E, Jia N, Fawcett H, Nardo T, Nakazawa Y, Lanzafame M, Moriwaki S, Sugita K, Kubota M, Obringer C, Spitz MA, Stefanini M, Laugel V, Orioli D, Ogi T, Lehmann A.
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Journal Title
Journal of Medical Genetics
Volume: 55
Issue: 5
Pages: 329-343
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] 乳がんにおけるDNA修復能の測定法の確立2021
Author(s)
田中 彩, 鈴木 啓司, 松瀬 美智子, 森田 道, 大坪 竜太, 松本 恵, 久芳 さやか, 及川 将弘, 矢野 洋, 江口 晋, 光武 範吏, 永安 武
Organizer
第29回 日本乳癌学会学術総会
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[Presentation] チェルノブイリと福島の甲状腺がんにおける様々な病理学的シナリオ2020
Author(s)
サエンコ ウラジミール, ボグダノワ タチアナ, 橋本 優子, 廣川 満良, リュドミラ ズルナドジ, 林 俊哲, 伊東 正博, 岩館 学, 光武 範吏, ログノビッチ タチアナ, 坂本 穆彦, 長沼 廣, 宮内 昭, トロンコ ミコラ, トマス ジュラルディン, 山下 俊一, 鈴木 眞一
Organizer
第63回 日本放射線影響学会 年次大会
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Invited
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[Presentation] 転写共役ヌクレオチド除去修復機構に重要なRNAポリメラーゼユビキチン化部位の同定2019
Author(s)
中沢由華, 原雄一郎, 岡泰由, 小峯起, Diana, van, den, Heuvel, 郭朝万, 大学保一, 磯野真由, 何予希, 嶋田繭子, 加藤香奈, 賈楠, 橋下悟, 小谷祐子, 三好由夏, 田中都, 祖父江顕, 光武範吏, 菅波孝祥, 増田章男, 大野欽司, 中田慎一郎, 真下知士, 山中宏二, Martijn, S., Luijsterburg, 荻朋男
Organizer
第42回日本分子生物学会年会
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[Presentation] ChIP-seqを利用したDNA損傷およびヌクレオチド除去修復のモニタリング2019
Author(s)
原雄一郎, 中沢由華, 岡泰由, 小峯起, Diana, van, den, Heuvel, 郭朝万, 大学保一, 磯野真由, 何予希, 嶋田繭子, 加藤香奈, 賈楠, 橋下悟, 小谷祐子, 三好由夏, 田中都, 祖父江顕, 光武範吏, 菅波孝祥, 増田章男, 大野欽司, 中田慎一郎, 真下知士, 山中宏二, Martijn, S., Luijsterburg, 荻朋男
Organizer
第42回日本分子生物学会年会
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