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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)531-541
Number of pages11
JournalEndocrine-Related Cancer
Volume24
Issue number10
DOIs
Publication statusPublished - Oct 2017

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Aldosterone
Adenoma
Mutation
Transcriptome
Gene Expression Profiling
Gene Expression
Hydrocortisone
Zona Glomerulosa
Glandular and Epithelial Neoplasms
Adrenal Cortex
DNA
Methylation
Cluster Analysis
Genome
RNA

All Science Journal Classification (ASJC) codes

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

Cite this

Murakami, M., Yoshimoto, T., Nakabayashi, K., Nakano, Y., Fukaishi, T., Tsuchiya, 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

Molecular characteristics of the KCNJ5 mutated aldosterone-producing adenomas. / 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.

In: Endocrine-Related Cancer, Vol. 24, No. 10, 10.2017, p. 531-541.

Research output: Contribution to journalArticle

Murakami, M, Yoshimoto, T, Nakabayashi, K, Nakano, Y, Fukaishi, T, Tsuchiya, K, Minami, I, Bouchi, R, Okamura, K, Fujii, Y, Hashimoto, K, Hata, KI, Kihara, K & Ogawa, Y 2017, 'Molecular characteristics of the KCNJ5 mutated aldosterone-producing adenomas', Endocrine-Related Cancer, vol. 24, no. 10, pp. 531-541. https://doi.org/10.1530/ERC-17-0117
Murakami M, Yoshimoto T, Nakabayashi K, Nakano Y, Fukaishi T, Tsuchiya K et al. Molecular characteristics of the KCNJ5 mutated aldosterone-producing adenomas. Endocrine-Related Cancer. 2017 Oct;24(10):531-541. https://doi.org/10.1530/ERC-17-0117
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. / Molecular characteristics of the KCNJ5 mutated aldosterone-producing adenomas. In: Endocrine-Related Cancer. 2017 ; Vol. 24, No. 10. pp. 531-541.
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