Analysis of radiation induced mutation patterns and frequencies with whole genome sequencing

• Project/Area Number: 15K16125
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Risk sciences of radiation and chemicals
• Research Institution: Hiroshima University
• Principal Investigator: Kanai Akinori 広島大学, 原爆放射線医科学研究所, 助教 (60549567)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 放射線 / 全ゲノム解析

Outline of Final Research Achievements

To estimate radiation induced mutation patterns and frequencies with whole genome sequencing, HT1080 single cells were gamma-irradiated 84 mGy, 390 mGy and 1885 mGy. The cells were cultured, DNA was extracted and we performed whole genome sequencing using HiSeq2500. Large deletions were rarely detected and there was no difference with dose dependent. The numbers of snps, small insertions and deletions were increased in 1885 mGy irradiated cell.

Research Products

• [Journal Article] A novel LSD1 inhibitor NCD38 ameliorates MDS-related leukemia with complex karyotype by attenuating leukemia programs via activating super-enhancers (2017)
  • Author(s): Sugino N, Kawahara M, Tatsumi G, Kanai A, Matsui H, Yamamoto R, Nagai Y, Fujii S, Shimazu Y, Hishizawa M, Inaba T, Andoh A, Suzuki T, Takaori-Kondo A.
  • Journal Title: Leukemia. Volume: in press Pages: 2303-2314
  • DOI: 10.1038/leu.2017.59
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Acquired expression ofCblQ367Pin mice induces dysplastic myelopoiesis mimicking chronic myelomonocytic leukemia (2017)
  • Author(s): Nakata Y, Ueda T, Nagamachi A, Yamasaki N, Ikeda KI, Sera Y, Takubo K, Kanai A, Oda H, Sanada M, Ogawa S, Tsuji K, Ebihara Y, Wolff L, Honda ZI, Suda T, Inaba T, Honda H.
  • Journal Title: Blood. Volume: 129 Pages: 2148-2160
  • DOI: 10.1182/blood-2016-06-724658
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Propagation of trimethylated H3K27 regulated by polycomb protein EED is required for embryogenesis, hematopoietic maintenance, and tumor suppression. (2016)
  • Author(s): Ueda T, Nakata Y, Nagamachi A, Yamasaki N, Kanai A, Matsui H, Honda ZI, Oda H, Wolff L, Inaba T, Honda H.
  • Journal Title: Proc Natl Acad Sci USA. Volume: 113(37) Pages: 10370-10375
  • DOI: 10.1073/pnas.1600070113
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Maintenance of the functional integrity of mouse hematopoiesis by EED and promotion of leukemogenesis by EED haploinsufficiency. (2016)
  • Author(s): Ikeda K-I, Ueda T, Yamasaki N, Nakata Y, Sera Y, Nagamachi A, Miyama T, Kobayashi H, TakuboK, Kanai A, Oda H, Wolff l, Honda Z-1, Ichinohe T, Matsubara A, Suda T, Inaba T, Honda H
  • Journal Title: Sci Rep. Volume: 6 Pages: 29454-29454
  • DOI: 10.1038/srep29454
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] The loss of Ezh2 drives the pathogenesis of myelofibrosis and sensitizes tumor-initiating cells to bromodomain inhibition. (2016)
  • Author(s): Sashida G, Wang S, Tomioka T, Oshima M, Kazumasa Aoyama K, Kanai A, Mochizuki-Kashio M, Harada H, Shimoda K, Iwama A.
  • Journal Title: J Exp Med. Volume: 213 Pages: 1459-1477
  • DOI: 10.1084/jem.20151121
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] ALK(R1275Q) perturbs extracellular matrix, enhances cell invasion and leads to the development of neuroblastoma in cooperation with MYCN. (2016)
  • Author(s): Ueda T, Nakata Y, Yamasaki N, Oda H, Sentani K, Kanai A, Onishi N, Ikeda K, Sera Y, Honda ZI, Tanaka K, Sata M, Ogawa S, Yasui W, Saya H, Takita J, Honda H.
  • Journal Title: Oncogene Volume: 無 Pages: 4447-4458
  • DOI: 10.1038/onc.2015.519
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] H-NS facilitates sequence diversification of horizontally transferred DNAs during their integration in host chromosomes (2016)
  • Author(s): Higashi K., Tobe T., Kanai A., Uyar E., Ishikawa S., Suzuki Y., Ogasawara N., Kurokawa K., and Oshima T
  • Journal Title: PLoS Genetics Volume: 12
  • DOI: 10.1371/journal.pgen.1005796
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] AF4 uses the SL1 components of RNAP1 machinery to initiate MLL fusion- and AEP-dependent transcription. (2015)
  • Author(s): Okuda H, Kanai A, Ito S, Matsui H, Yokoyama A.
  • Journal Title: Nat Commun. Volume: 23;6
  • DOI: 10.1038/ncomms9869
  • NAID: 120005672585
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Fbxl10 overexpression in murine hematopoietic stem cells induces leukemia involving metabolic activation and upregulation of Nsg2 (2015)
  • Author(s): Ueda T, Nagamachi A, Takubo K, Yamasaki N, Matsui H, Kanai A, Nakata Y, Ikeda K Konuma T, Oda H, Wolff L, Honda Z, Wu X, Helin K, Iwama A, Suda T, Inaba T, Honda H.
  • Journal Title: Blood. Volume: 125 Pages: 3437-3446
  • DOI: 10.1182/blood-2014-03-562694
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Analysis of radiation induced mutations using next generation sequencer. (2017)
  • Author(s): Akinori Kanai, Akiko Nagamachi, Hidehiko Kawai, Hirotaka Matsui, Kenji Kamiya, Toshiya Inaba
  • Organizer: 放射線災害・医科学研究拠点 第 1 回国際シンポジウム
  • Place of Presentation: 広島市 広島大学
  • Year and Date: 2017-02-21
• [Presentation] 次世代シーケンサーを用いた放射線誘発変異解析 (2016)
  • Author(s): 金井昭教、長町安希子、河合秀彦、松井啓隆、神谷研二、稲葉俊哉
  • Organizer: 第39回日本分子生物学会
  • Place of Presentation: 横浜市 パシフィコ横浜 広島市
  • Year and Date: 2016-11-30
• [Presentation] 次世代シーケンサーを用いた放射線誘発変異解析 (2016)
  • Author(s): 金井昭教、長町安希子、河合秀彦、松井啓隆、神谷研二、稲葉俊哉
  • Organizer: 日本放射線影響学会第59回大会
  • Place of Presentation: JMSアステールプラザ
  • Year and Date: 2016-10-26
• [Presentation] 次世代シーケンサーを用いた放射線誘発変異解析 (2015)
  • Author(s): 金井昭教、長町安希子、河合秀彦、松井啓隆、神谷研二、稲葉俊哉
  • Organizer: 第４０回中国地区放射線影響研究会
  • Place of Presentation: 広島大学
  • Year and Date: 2015-07-17
• [Presentation] 次世代シーケンサーを用いた放射線誘発変異解析 (2015)
  • Author(s): 金井昭教、長町安希子、河合秀彦、松井啓隆、神谷研二、稲葉俊哉
  • Organizer: NGS現場の会第四回研究会
  • Place of Presentation: つくば国際会議場
  • Year and Date: 2015-07-01
• [Presentation] Analysis of radiation induced mutations using next generation sequencer. (2015)
  • Author(s): Akinori Kanai, Akiko Nagamachi, Hidehiko Kawai, Hirotaka Matsui, Kamiya Kenji, Toshiya Inaba
  • Organizer: 15th International Congress of Radiation Research (ICRR)
  • Place of Presentation: Kyoto International Conference Center
  • Year and Date: 2015-05-25
  • Int'l Joint Research