2018 Fiscal Year Final Research Report
Genomics in primary aldosteronism
Project/Area Number |
16K08962
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Laboratory medicine
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Research Institution | Tokyo Medical and Dental University |
Principal Investigator |
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Research Collaborator |
Hata Kenichiro
Kihara Kazunori
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Project Period (FY) |
2016-04-01 – 2019-03-31
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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.
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Free Research Field |
内分泌代謝学
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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。
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