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The mutations in DDX3X affect sex-biased cancer occurrence

Research Project

Project/Area Number 16K08673
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Human pathology
Research InstitutionSaitama Medical University

Principal Investigator

Momose Shuji  埼玉医科大学, 医学部, 准教授 (70360344)

Co-Investigator(Kenkyū-buntansha) 田丸 淳一  埼玉医科大学, 医学部, 教授 (30188429)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsリンパ腫 / バーキットリンパ腫 / DDX3X / がんの性差 / Burkittリンパ腫 / がん抑制遺伝子 / がん / 性差 / 癌 / 疾患モデル
Outline of Final Research Achievements

A subset of cancer harbors mutations in DDX3X and we identified DDX3X mutations in B cell lymphoma from our previous genetic screening. Though some types of cancer present sex-bias in its incidence, its underlying mechanism of sex-bias was not elucidated except for the involvement of sex hormone-related cancers. To explore the sex-biased cancer occurrence in the aspect of gene function, we analyzed DDX3X in B cell lymphoma cell lines that harbor DDX3X mutations. Finally we elucidated that wild type DDX3X suppressed PI3K pathway and DDX3X acts as tumor suppressor gene. Also DDX3X located in X-chromosome and reported that it escapes from X chromosomal inactivation. Therefore, the occurrence of DDX3X mutations in male than in female can easily to provoke genetic inactivation as male possess only one X chromosome.

Academic Significance and Societal Importance of the Research Achievements

一部のがん種では男女差がみられるが、性ホルモンが関わるがん種以外では、男女差がなぜ生じるかはわかっていない。本研究では性ホルモンの関与が低いがん種での男女差の機構として、遺伝子の存在する染色体としての性染色体に注目した。
常染色体では通常、2つの相同な遺伝子2つが存在し、がん抑制遺伝子では2つの遺伝子が傷害され初めて機能が喪失する。一方性染色体では、X染色体は女性で2本あるものの男性では1本しかなく、X染色体上に存在するがん抑制遺伝子に関しては男性は女性に比べて遺伝子の機能喪失に陥る可能性が高く、こうした機構ががんの男女差を生じさせている可能性が本研究により示された。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (21 results)

All 2019 2018 2017 2016 Other

All Int'l Joint Research (1 results) Journal Article (7 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results) Presentation (8 results) Book (5 results)

  • [Int'l Joint Research] University of Wuerzburg(Germany)

    • Related Report
      2016 Research-status Report
  • [Journal Article] Clinicopathological features of clinical methotrexate-related lymphoproliferative disorders2019

    • Author(s)
      Tokuhira M, Saito S, Suzuki K, Higashi M, Momose S, Shimizu T, Mori T, Kimura Y, Amano K, Okamoto S, Takeuchi T, Tamaru JI, Kizaki M
    • Journal Title

      Leuk Lymphoma

      Volume: - Issue: 10 Pages: 1-8

    • DOI

      10.1080/10428194.2019.1585841

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Anaplastic large cell lymphoma with TP63 rearrangement: A dismal prognosis.2019

    • Author(s)
      Yamashita T, Higashi M, Kawano R, Momose S, Tokuhira M, Kizaki M, Tamaru JI
    • Journal Title

      Pathol Int

      Volume: 69(3) Issue: 3 Pages: 155-159

    • DOI

      10.1111/pin.12758

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Human parvovirus B19-induced hemophagocytic lymphohistiocytosis and myocarditis in an adult patient with hereditary spherocytosis2018

    • Author(s)
      Tanaka Y, Takahashi Y, Kimura Y, Tomikawa T, Anan T, Sagawa M, Tabayashi T, Watanabe R, Tokuhira M, Momose S, Tamaru JI, Kizaki M
    • Journal Title

      Rinsho Ketsueki

      Volume: 59 Issue: 6 Pages: 682-687

    • DOI

      10.11406/rinketsu.59.682

    • NAID

      130007393801

    • ISSN
      0485-1439, 1882-0824
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinicopathologic investigation of methotrexate-induced lymphoproliferative disorder, with a focus on regression.2017

    • Author(s)
      Tokuhira M, Saito S, Okuyama A, Suzuki K, Higashi M, Momose S, Shimizu T, Mori T, Anan-Nemoto T, Amano K, Okamoto S, Takeuchi T, Tamaru JI, Kizaki M.
    • Journal Title

      Leuk Lymphoma

      Volume: Sep.10 Issue: 5 Pages: 1-10

    • DOI

      10.1080/10428194.2017.1369073

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] The aggressive clinical courses of Hodgkin lymphoma primarily diagnosed as methotrexate-induced non-specific lymphoproliferative disorder in patients with rheumatoid arthritis2017

    • Author(s)
      Tokuhira M, Tabayashi T, Tanaka Y, Takahashi Y, Kimura Y, Tomikawa T, Anan-Nemoto T, Momose S, Higashi M, Okuyama A, Watanabe R, Amano K, Tamaru JI, Kizaki M.
    • Journal Title

      Journal of Clinical and Experimental Hematopathology

      Volume: 56 Issue: 3 Pages: 165-169

    • DOI

      10.3960/jslrt.56.165

    • NAID

      130005465213

    • ISSN
      1346-4280, 1880-9952
    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Nuclear expression of Y box binding-1 is important for resistance to chemotherapy2017

    • Author(s)
      Takahisa Yamashita, Morihiro Higashi, Shuji Momose, Makoto Morozumi, Jun-Ichi Tamaru
    • Journal Title

      International Journal of Oncology

      Volume: 51 Issue: 2 Pages: 579-586

    • DOI

      10.3892/ijo.2017.4031

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] 免疫チェックポイント阻害薬の耐性機序2017

    • Author(s)
      百瀬修二
    • Journal Title

      血液内科

      Volume: 75 Pages: 755-759

    • NAID

      40021421905

    • Related Report
      2017 Research-status Report
  • [Presentation] High grade B-cell lymphoma の病理診断 - 血液病理医の立場から2018

    • Author(s)
      百瀬修二、田丸淳一
    • Organizer
      第 65 回日本臨床検査医学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] リンパ腫におけるとゲノム異常と形態像の連関2018

    • Author(s)
      百瀬修二、田丸淳一
    • Organizer
      第50回日本臨床分子形態学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 免疫不全関連リンパ増殖性疾患2018

    • Author(s)
      百瀬修二、田丸淳一
    • Organizer
      第107回日本病理学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Burkitt リンパ腫の遺伝子異常とその分子生物学的意義2017

    • Author(s)
      百瀬修二
    • Organizer
      第3 回リンパ腫分子病態研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] 高悪性度B細胞リンパ腫の変更点2017

    • Author(s)
      百瀬修二,大澤久美子,大野優子,青木智章,田丸淳一
    • Organizer
      第56回日本臨床細胞学会秋期大会
    • Related Report
      2017 Research-status Report
  • [Presentation] CD30-positive B-cell lymphoma2017

    • Author(s)
      百瀬修二,田丸淳一
    • Organizer
      第20回日本血液病理研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] Genetics and pathological aspects of MYC-positive high grade B-cell lymphoma2017

    • Author(s)
      Momose S, Tamaru JI
    • Organizer
      The 106th Annual Meeting of the Japanese Society of Pathology
    • Related Report
      2017 Research-status Report
  • [Presentation] 蛍光ナノ粒子を用いた MYCタンパク発現検出系の構築とその臨床病理学的意義2016

    • Author(s)
      百瀬修二、菊地 淳、高柳奈津子、田丸淳一
    • Organizer
      第105回日本病理学会総会
    • Place of Presentation
      仙台
    • Year and Date
      2016-05-13
    • Related Report
      2016 Research-status Report
  • [Book] ALK陽性大細胞型B細胞リンパ腫, WHO分類改訂第4版による白血病・リンパ系腫瘍の病態学2019

    • Author(s)
      百瀬修二, 田丸淳一
    • Total Pages
      527
    • Publisher
      中外医学社
    • Related Report
      2018 Annual Research Report
  • [Book] リンパ腫アトラス第5版2018

    • Author(s)
      百瀬修二、田丸淳一
    • Total Pages
      448
    • Publisher
      文光堂
    • Related Report
      2018 Annual Research Report
  • [Book] 血液内科グリーンノート2017

    • Author(s)
      百瀬修二
    • Total Pages
      410
    • Publisher
      中外医学社
    • ISBN
      9784498225060
    • Related Report
      2017 Research-status Report
  • [Book] リンパ腫の病理診断2016

    • Author(s)
      百瀬修二、田丸淳一
    • Total Pages
      6
    • Publisher
      科学評論社
    • Related Report
      2016 Research-status Report
  • [Book] DLBCLの中枢原発のリスクとしてのMYC/BCL2発現2016

    • Author(s)
      百瀬修二
    • Total Pages
      6
    • Publisher
      科学評論社
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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