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Identification of mutated splicing factor target genes

Research Project

Project/Area Number 26640075
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Tumor biology
Research InstitutionNational Hospital Organization Nagoya Medical Center (2015)
Kyoto University (2014)

Principal Investigator

SANADA MASASHI  独立行政法人国立病院機構(名古屋医療センター臨床研究センター), その他部局等, その他 (20529044)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords骨髄異形成症候群 / MDS / RNAスプライシング / RNAシーケンス
Outline of Final Research Achievements

Although splicing factor mutations are the most important genetic alterations in MDS, little is known about exact gene targets whose abnormal splicing is responsible for the pathogenesis of MDS. SF3B1 and SRSF2 mutations were associated with distinct clinical phenotypes and outcomes together with RNA splicing. To explore the molecular basis of these distinct features in terms of splicing alterations, RNA sequencing data from SF3B1-mutated and SRSF2-mutated bone marrow hematopoietic cells were compared with those without known splicing factor mutations to detect splicing events significantly enriched in splicing factor mutated cases. SF3B1 mutations caused misrecognition of 3’ splice sites of several genes, which included one of the causative genes for congenital sideroblastic anemia. On the other hand, SRSF2 mutations were characterized by modest but more widespread alterations in exon usage of genes. Our results provide insights into the pathogenesis of splicing factor mutated MDS.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (8 results)

All 2015 2014

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (4 results) (of which Invited: 1 results) Book (1 results)

  • [Journal Article] Aberrant splicing of U12-type introns is the hallmark of ZRSR2 mutant myelodysplastic syndrome.2015

    • Author(s)
      Madan V, Kanojia D, Li J, Okamoto R, Sato-Otsubo A, Kohlmann A, Sanada M, Grossmann V, Sundaresan J, Shiraishi Y, Satoru M, Thol F, Ganser A, Yang H, Haferlach T, Ogawa S, Koeffler HP
    • Journal Title

      Nature Commun.

      Volume: 6 Issue: 1 Pages: 6042-6042

    • DOI

      10.1038/ncomms7042

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Recurrent somatic mutations underlie corticotropin-independent Cushing's syndrome.2014

    • Author(s)
      7.Sato Y, Maekawa S, Ishii R, Sanada M, Morikawa T, Shiraishi Y, Yoshida K, Nagata Y, Sato-Otsubo A, Yoshizato T, Suzuki H, Shiozawa Y, Kataoka K, Kon A, Aoki K, Chiba K, Tanaka H, Kume H, Miyano S, Fukayama M, Nureki O, Homma Y, Ogawa S.
    • Journal Title

      Science

      Volume: 344 Issue: 6186 Pages: 917-920

    • DOI

      10.1126/science.1252328

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Haploinsufficiency of Sf3b1 leads to compromised stem cell function but not to myelodysplasia.2014

    • Author(s)
      Matsunawa M, Yoshida K
    • Journal Title

      Leukemia

      Volume: (Epub ahead of print) Issue: 9 Pages: 1-7

    • DOI

      10.1038/leu.2014.73

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] クローン解析に基づく造血器腫瘍の病態理解2015

    • Author(s)
      真田 昌
    • Organizer
      日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-10-09
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Comprehensive Analysis of Alternative RNA Splicing in Myelodysplastic Syndrome2014

    • Author(s)
      Yusuke Shiozawa, Sato Sato-Otsubo, Anna Gallì, Kenichi Yoshida, Tetsuichi Yoshizato, Yusuke Sato, Keisuke Kataoka,Masashi Sanada,Yuichi Shiraishi, Kenichi Chiba, Satoru Miyano, Luca Malcovati, Mario Cazzola, and Seishi Ogawa
    • Organizer
      55th American Society of Hematology 2014 Annual Meeting
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2014-12-06 – 2014-12-09
    • Related Report
      2014 Research-status Report
  • [Presentation] ZRSR2 Mutations Cause Dysregulated RNA Splicing in MDS2014

    • Author(s)
      Vikas Madan, Deepika Kanojia, Li Jia, Ryoko Okamoto, Aiko Sato-Otsubo, Alexander Kohlmann, Masashi Sanada, Vera Grossmann, Janani Sundaresan, Yuichi Shiraishi, Satoru Miyano, Felicitas Thol, Arnold Ganser, Henry Yang, Torsten Haferlach, Seishi Ogawa, and H. Phillip Koeffler
    • Organizer
      55th American Society of Hematology 2014 Annual Meeting
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2014-12-06 – 2014-12-09
    • Related Report
      2014 Research-status Report
  • [Presentation] SF3B1 PLAYS AN IMPORTANT ROLE IN THE REGULATION OF HEMATOPOIETIC STEMS CELLS, BUT HAPLOINSUFFICIENCY OF SF3B1 MAY NOT BE SOLELY RESPONSIBLE FOR MYELODYSPLASIA2014

    • Author(s)
      Manabu Matsunawa, Ryo Yamamoto, Masashi Sanada, Ayana Kon, Aiko Sato-Otsubo, Yusuke Shiozawa, Kenichi Yoshida, Yasunobu Nagata, Tetsuichi Yoshizato, Makoto Otsu, Kyoichi Isono, Haruhiko Koseki, Hiromitsu Nakauchi, Seishi Ogawa
    • Organizer
      The 19th Congress of European Hematology Association
    • Place of Presentation
      Milan, Italy
    • Year and Date
      2014-06-12 – 2014-06-15
    • Related Report
      2014 Research-status Report
  • [Book] 医学のあゆみVol.249 No.10特集 がんゲノム研究の進歩ー網羅的解析からの知見 医歯薬出版 「造血器腫瘍におけるゲノム解析と臨床への展開」2014

    • Author(s)
      眞田 昌
    • Total Pages
      129
    • Publisher
      医歯薬出版
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2017-05-10  

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