Molecular characteristics of the KCNJ5 mutated aldosterone-producing adenomas

Masanori Murakami, Takanobu Yoshimoto, Kazuhiko Nakabayashi, Yujiro Nakano, Takahiro Fukaishi, Kyoichiro Tsuchiya, Isao Minami, Ryotaro Bouchi, Kohji Okamura, Yasuhisa Fujii, Koshi Hashimoto, Ken Ichiro Hata, Kazunori Kihara, Yoshihiro Ogawa

研究成果: ジャーナルへの寄稿記事

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The pathophysiology of aldosterone-producing adenomas (APAs) has been investigated via genetic approaches and the pathogenic significance of a series of somatic mutations, including KCNJ5, has been uncovered. However, how the mutational status of an APA is associated with its molecular characteristics, including its transcriptome and methylome, has not been fully understood. This study was undertaken to explore the molecular characteristics of APAs, specifically focusing on APAs with KCNJ5 mutations as opposed to those without KCNJ5 mutations, by comparing their transcriptome and methylome status. Cortisol-producing adenomas (CPAs) were used as reference. We conducted transcriptome and methylome analyses of 29 APAs with KCNJ5 mutations, 8 APAs without KCNJ5 mutations and 5 CPAs. 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 depending 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 that from normal adrenal cortex obtained from the Gene Expression Omnibus suggested similarities between APAs with KCNJ5 mutations and zona glomerulosa. The present study, which is based on transcriptome and methylome analyses, indicates the molecular heterogeneity of APAs depends on their mutational status. Here, we report the unique characteristics of APAs with KCNJ5 mutations.

元の言語英語
ページ(範囲)531-541
ページ数11
ジャーナルEndocrine-Related Cancer
24
発行部数10
DOI
出版物ステータス出版済み - 10 2017

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Oncology
  • Endocrinology
  • Cancer Research

フィンガープリント Molecular characteristics of the KCNJ5 mutated aldosterone-producing adenomas' の研究トピックを掘り下げます。これらはともに一意のフィンガープリントを構成します。

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    Murakami, M., Yoshimoto, T., Nakabayashi, K., Nakano, Y., Fukaishi, T., Tsuchiya, K., Minami, I., Bouchi, R., Okamura, K., Fujii, Y., Hashimoto, K., Hata, K. I., Kihara, K., & Ogawa, Y. (2017). Molecular characteristics of the KCNJ5 mutated aldosterone-producing adenomas. Endocrine-Related Cancer, 24(10), 531-541. https://doi.org/10.1530/ERC-17-0117