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Genomics in primary aldosteronism

Research Project

Project/Area Number 16K08962
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Laboratory medicine
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Yoshimoto Takanobu  東京医科歯科大学, 医学部附属病院, 講師 (80297457)

Research Collaborator Hata Kenichiro  
Kihara Kazunori  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsアルドステロン / 副腎腫瘍
Outline of Final Research Achievements

We conducted transcriptome and methylome analyses of 29 aldosterone-producintg adenomas (APAs) with KCNJ5 mutations, 8 APAs without KCNJ5 mutations, and 5 cortisol-producing adenomas. Genome-wide gene expression and CpG methylation profiles were obtained from RNA and DNA samples extracted from these 42 adrenal tumors. Cluster analysis of the transcriptome and methylome revealed molecular heterogeneity in APAs depends on their mutational status. DNA hypomethylation and gene expression changes in Wnt signaling and inflammatory response pathways were characteristic of APAs with KCNJ5 mutations. Comparisons between transcriptome data from our APAs and data from normal adrenal cortex obtained from the Gene Expression Omnibus suggested similarities between APAs with KCNJ5 mutations and zona glomerulosa. The present study indicates the molecular heterogeneity of APAs depends on their mutational status.

Academic Significance and Societal Importance of the Research Achievements

ホルモン産生副腎皮質腫瘍のうち原発性アルドステロン症(PA)、Cushing 症候群(CS)は多様な心血管系・代謝系の合併症を生じ、またPA は高血圧の約10%、CS はサブクリニカルなものも含めると副腎偶発腫の約8.5%と頻度も高く、臨床的に重要である。本研究により本邦のアルドステロン産生腺腫の7割を占めるKCNJ5変異陽性腫瘍は腫瘍全ゲノムの低メチル化とそれに関連した特異な遺伝子発現を示したことから、DNAメチル化異常といった後天的エピゲノム要因が本腫瘍の発生に関与することが示唆され、内分泌腫瘍の発症メカニズムの一端が示された。

Report

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

    (6 results)

All 2018 2017 2016

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Acknowledgement Compliant: 1 results) Presentation (3 results) (of which Invited: 1 results)

  • [Journal Article] Effect of Eplerenone on the Glomerular Filtration Rate (GFR) in Primary Aldosteronism: Sequential Changes in the GFR During Preoperative Eplerenone Treatment to Subsequent Adrenalectomy2018

    • Author(s)
      Nakano Yujiro、Yoshimoto Takanobu、Fukuda Tatsuya、Murakami Masanori、Bouchi Ryotaro、Minami Isao、Hashimoto Koshi、Fujii Yasuhisa、Kihara Kazunori、Ogawa Yoshihiro
    • Journal Title

      Internal Medicine

      Volume: 57 Issue: 17 Pages: 2459-2466

    • DOI

      10.2169/internalmedicine.0438-17

    • NAID

      130007480026

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2018-09-01
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular characteristics of the KCNJ5 mutated aldosterone-producing adenomas2017

    • Author(s)
      Murakami Masanori、Yoshimoto Takanobu、Nakabayashi Kazuhiko、Nakano Yujiro、Fukaishi Takahiro、Tsuchiya Kyoichiro、Minami Isao、Bouchi Ryotaro、Okamura Kohji、Fujii Yasuhisa、Hashimoto Koshi、Hata Ken-ichiro、Kihara Kazunori、Ogawa Yoshihiro
    • Journal Title

      Endocrine-Related Cancer

      Volume: 24 Issue: 10 Pages: 531-541

    • DOI

      10.1530/erc-17-0117

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Expression of inflammation-related genes in aldosterone-producing adenomas with KCNJ5 mutation.2016

    • Author(s)
      Murakami M, Yoshimoto T, Nakano Y, Tsuchiya K, Minami I, Bouchi R, Fujii Y, Nakabayashi K, Hashimoto K, Hata K, Kihara K, Ogawa Y.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 476 Issue: 4 Pages: 614-619

    • DOI

      10.1016/j.bbrc.2016.06.007

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] アルドステロン産生腺腫(APA)のゲノム・エピゲノム解析2018

    • Author(s)
      吉本貴宣
    • Organizer
      第91回日本内分泌学会学術総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] ゲノム・エピゲノム解析からみた原発性アルドステロン症(APA)の多様性2017

    • Author(s)
      吉本貴宣、村上正憲、中野雄二郎、小川佳宏
    • Organizer
      第90回日本内分泌学会学術総会
    • Place of Presentation
      京都市勧業館みやこめっせ
    • Year and Date
      2017-04-20
    • Related Report
      2016 Research-status Report
  • [Presentation] アルドステロン産生腺腫(APA)のゲノミクス2017

    • Author(s)
      吉本貴宣
    • Organizer
      心血管代謝週間CVMW2017
    • Related Report
      2017 Research-status Report

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

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