Elucidation of the mechanism of cancer-related gene fusion using CRISPR/Cas9

• Project/Area Number: 15K00542
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Risk sciences of radiation and chemicals
• Research Institution: Nagasaki University
• Principal Investigator: YAMAUCHI Motohiro 長崎大学, 原爆後障害医療研究所, 助教 (60437910)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 融合遺伝子 / 癌 / CRISPR/Cas9 / DNA二本鎖切断 / DNA修復 / DNA-PKcs

Outline of Final Research Achievements

The goal of this study was to establish a quantitative assay for the frequency of cancer-related fusion gene generated by CRISPR/Cas9, and to identify factors affecting gene fusion frequency. Our achievement is (1) establishment of an assay that quantifies the frequency of lung cancer-related EML4-ALK fusion gene by digital PCR, and (2) identification of DNA-PKcs protein as an important factor for the gene fusion.

Research Products

• [Journal Article] Regulation of pairing between broken DNA-containing chromatin regions by Ku80, DNA-PKcs, ATM, and 53BP1 (2017)
  • Author(s): Motohiro Yamauchi, Atsushi Shibata, Keiji Suzuki, Masatoshi Suzuki, Atsuko Niimi, Hisayoshi Kondo, Miwa Miura, Miyako Hirakawa, Keiko Tsujita, Shunichi Yamashita, Naoki Matsuda
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 41812-41812
  • DOI: 10.1038/srep41812
  • NAID: 120006987560
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Regulation of pairing between broken DNA-containing chromatin regions by Ku80, DNA-PKcs, ATM, and 53BP1. (2017)
  • Author(s): 山内基弘、柴田淳史、鈴木啓司、鈴木正敏、新美敦子、近藤久義、三浦美和、平川美弥子、辻田啓子、山下俊一、松田尚樹
  • Organizer: Ataxia Telangiectasia Workshop 2017
  • Place of Presentation: ミラノ（イタリア）
  • Int'l Joint Research
• [Presentation] CRISPR/Cas9を用いた癌関連融合遺伝子の生成頻度の定量アッセイの樹立 (2016)
  • Author(s): 山内基弘
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
• [Presentation] Establishment of a novel quantitative assay for cancer-related gene fusion using CRISPR/Cas9 (2016)
  • Author(s): 山内基弘、平川美弥子、辻田啓子、松田尚樹
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
• [Presentation] ATM and DNA-PKcs suppress pairing between multiple DNA double-strand breaks (2015)
  • Author(s): 山内基弘、鈴木啓司、柴田淳史、新美敦子、鈴木正敏、近藤久義、三浦美和、平川美弥子、山下俊一、松田尚樹
  • Organizer: 第38回日本分子生物学会年会
  • Place of Presentation: 神戸ポートアイランド（兵庫県神戸市）
  • Year and Date: 2015-12-03
• [Presentation] ATMとDNA-PKcsによるDNA二本鎖切断同士の会合の抑制 (2015)
  • Author(s): 山内基弘、柴田淳史、鈴木啓司
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-10-08
• [Presentation] Factors affecting interaction between multiple DNA double-strand breaks (2015)
  • Author(s): 山内基弘、鈴木啓司、柴田淳史、鈴木正敏、近藤久義、三浦美和、平川美弥子、山下俊一、松田尚樹
  • Organizer: 15th International Congress of Radiation Research
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Year and Date: 2015-05-26
  • Int'l Joint Research