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Molecular-cytogenetic studies of PVT1 rearrangements in hematological malignancies

Research Project

Project/Area Number 25461432
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Hematology
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Taniwaki Masafumi  京都府立医科大学, 医学(系)研究科(研究院), 教授 (80163640)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
KeywordsPVT1遺伝子 / キメラmRNA / 遺伝子増幅 / 骨髄性白血病 / NSMCE2 / クロモスリプシス / 8q24増幅 / 急性骨髄性白血病 / Linc RNA / PVT1 / 血液腫瘍 / キメラ転写産物
Outline of Final Research Achievements

Specific chromosomal translocations in hematological malignancies are a clue of identifying rearranged gene at the region of breakpoints. To gain insight into the role(s) of dmins, we cytogenetically and molecularly analyzed 8q24 amplicons in acute myelogenous leukemia (AML) patient-derived leukemic cells and AML-derived cell line (HL60), identifying fusion transcripts between PVT1 exon 1a and NSMCE2 exon 3 in the patient, and a fusion gene between exon 6 of NSMCE2 and exon 1 of BF104016, a noncoding RNA sharing the sequence of CCDC26 exon 4. These novel chimeric RNAs, PVT1-NSMCE2 and CCDC26-NSMCE2, were identified in association with dmins showing 8q24 amplicons. Chromothripsis is a possible cytogenetic mechanism of generating these novel chimeric genes. PVT1 and CCDC26 are long intergenic non-coding RNAs (lincRNAs). Our study suggests that the fusion genes involving lincRNAs potentially plays as-yet-unknown oncogenic functional roles.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (11 results)

All 2016 2015 2014 2013

All Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (5 results)

  • [Journal Article] Recurrent DUX4 fusions in B cell acute lymphoblastic leukemia of adolescents and young adults2016

    • Author(s)
      Takahiko Yasuda, Shinobu Tsuzuki, Masahito Kawazu, Fumihiko Hayakawa, Shinya Kojima, Toshihide Ueno, Naoto Imoto, Shinji Kohsaka, Akiko Kunita, Koichiro Doi, Toru Sakura, Toshiaki Yujiri, Eisei Kondo, Katsumichi Fujimaki, Yasunori Ueda, Yasutaka Aoyama, Shigeki Ohtake, Junko Takita, Eirin Sai, Masafumi Taniwaki, et al.
    • Journal Title

      Nature genetics

      Volume: in press Issue: 5 Pages: 409-417

    • DOI

      10.1038/ng.3535

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Loss of RUNX1/AML1 arginine-methylation impairs peripheral T cell homeostasis.2015

    • Author(s)
      Mizutani S, Yoshida T, Zhao X, Nimer SD, Taniwaki M, Okuda T.
    • Journal Title

      Br J Haematol

      Volume: 170 Pages: 859-873

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 8q24 amplified segments involve novel fusion genes between NSMCE2 and long noncoding RNAs in acute myelogenous leukemia.2014

    • Author(s)
      Chinen Y, Sakamoto N, Nagoshi H, Taki T, Maegawa S, Tatekawa S, Tsukamoto T, Mizutani S, Shimura Y, Yamamoto-Sugitani M, Kobayashi T, Matsumoto Y, Horiike S, Kuroda J, Taniwaki M.
    • Journal Title

      J Hematol Oncol

      Volume: 7 Issue: 1 Pages: 68-68

    • DOI

      10.1186/s13045-014-0068-2

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The leucine twenty homeobox (LEUTX) gene, which lacks a histone acetyltransferase domain, is fused to KAT6A in therapy-related AML with t(8;19)(p11;q13).2014

    • Author(s)
      Chinen Y, Taki T, Tsutsumi Y, Kobayashi S, Matsumoto Y, Sakamoto N, Kuroda J, Horiike S, Nishida K, Ohno H, Uike N, Taniwaki M.
    • Journal Title

      Genes Chromosomes Cancer

      Volume: 53 Issue: 4 Pages: 299-308

    • DOI

      10.1002/gcc.22140

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identification of novel fusion genes with 28S ribosomal DNA in hematologic malignancies.2014

    • Author(s)
      Kobayashi S, Taki T, Nagoshi H, Chinen Y, Yokokawa Y, Kanegane H, Matsumoto Y, Kuroda J, Horiike S, Nishida K, Taniwaki M.
    • Journal Title

      Int J Oncol

      Volume: 44 Issue: 4 Pages: 1193-1198

    • DOI

      10.3892/ijo.2014.2291

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] NS-018, a selective JAK2 inhibitor, preferentially inhibits CFU-GM colony formation by bone marrow mononuclear cells from high-risk myelodysplastic syndrome patients.2014

    • Author(s)
      Kuroda J, Kodama A, Chinen Y, Shimura Y, Mizutani S, Nagoshi H, Kobayashi T, Matsumoto Y, Nakaya Y, Tamura A, Kobayashi Y, Naito H, Taniwaki M.
    • Journal Title

      Leuk Res.

      Volume: 38 Issue: 5 Pages: 619-624

    • DOI

      10.1016/j.leukres.2014.03.001

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] PVT1-NSMCE2 fusion gene enhances BCL-X expression and drug resistance in leukemic cells.2014

    • Author(s)
      Chinen Y, Sakamoto N, Nagoshi H, Taki T, Kobayashi S, Nishida K, Maegawa S, Kiyota M, Mizutani S, Shimura Y, Sugitani M, Kobayashi T, Matsumoto Y, Horiike S, Kuroda J, Tniwaki M.
    • Organizer
      第76回日本血液学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2014-10-31
    • Related Report
      2014 Research-status Report
  • [Presentation] Novel fusion genes, PVT1-NSMCE2 and CCDC26-NSMCE in acute myeloid leukemia harboring 8q24 amplicons.2014

    • Author(s)
      Chinen Y, Sakamoto N, Nagoshi H, Taki T, Kobayashi T, Nishida K, Maegawa S, Kiyota M, Mizutani S, Shimura Y, Yamamoto-Sugitani M, Matsumoto Y, Horiike S, Kuroda J, Taniwaki M.
    • Organizer
      The 5th JSH International Symposium 2014
    • Place of Presentation
      Hmamatsu
    • Year and Date
      2014-05-24
    • Related Report
      2014 Research-status Report
  • [Presentation] Identification of novel fusion transcripts involving NSMCE2 in acute myeloid leukemia harboring 8q24 amplification2013

    • Author(s)
      Sakamoto N, Chinen Y, Nagoshi H, Taki T, Kobayashi S, Nishida K, Sugitani M, Kobayashi T, Matsumoto Y, Horiike S, Taniwaki M
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] Identification of novel fusion of NSMCE2 in acute myeloid leukemia harboring 8q24 amplification2013

    • Author(s)
      Chinen Y, Sakamoto N, Nagoshi H, Taki T, Kobayashi S, Nishida K, Nakayama R, Mizutani S, Shimura Y, Kiyota M, Sugitani M, Kobayashi T, Matsumoto Y, Kuroda J, Horiike S, Taniwaki M
    • Organizer
      第75回日本血液学会学術集会
    • Place of Presentation
      札幌
    • Related Report
      2013 Research-status Report
  • [Presentation] Novel Fusion Transcripts PVT1-NSMCE2 and BF104016-NSMCE2 Resulting In Depletion Of NSMCE2 Protein In Acute Myeloid Leukemia Harboring 8q24 Amplicons2013

    • Author(s)
      Chinen Y, Sakamoto N, Nagoshi H, Taki T, Kobayashi S, Nishida K, Maegawa S, Nakayama R, Kiyota M, Mizutani S, Shimura Y, Yamamoto-Sugitani M, Kobayashi T, Matsumoto Y, Yokota S, Kuroda J, Horiike S, Taniwaki M
    • Organizer
      55th ASH Annual Meeting
    • Place of Presentation
      New Orleans, LA, USA
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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