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Integration of transcriptome and methylome analysis of aldosterone-producing adenomas
Masanori Murakami1, Takanobu Yoshimoto2, Kazuhiko Nakabayashi1
1Department of Molecular Endocrinology and MetabolismGraduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, JapanDepartment of Maternal-Fetal BiologyNational Research Institute for Child Health and Development, Tokyo 157-8535, JapanCenter for Medical Welfare and Liaison ServicesDepartments of UrologyPreemptive Medicine and MetabolismOrgan Network and MetabolismGraduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, JapanJapan Science and Technology AgencyPRESTO, Tokyo 102-0076, JapanJapan Science and Technology AgencyCREST, Tokyo 102-0076, Japan.
Objective:
The pathophysiology of aldosterone-producing adenomas (APA) has been investigated intensively through genetic and genomic approaches. However, the role of epigenetics in APA is not fully understood. In the present study, we explored the relationship between gene expression and DNA methylation status in APA.
Methods:
We conducted an integrated analysis of transcriptome and methylome data of paired APA-adjacent adrenal gland (AAG) samples from the same patient. The adrenal specimens were obtained from seven Japanese patients with APA who underwent adrenalectomy. Gene expression and genome-wide CpG methylation profiles were obtained from RNA and DNA samples that were extracted from those seven paired tissues.
Results:
Methylome analysis showed global CpG hypomethylation in APA relative to AAG. The integration of gene expression and methylation status showed that 34 genes were up-regulated with CpG hypomethylation in APA. Of these, three genes (CYP11B2, MC2R, and HPX) may be related to aldosterone production, and five genes (PRRX1, RAB38, FAP, GCNT2, and ASB4) are potentially involved in tumorigenesis.
Conclusion:
The present study is the first methylome analysis to compare APA with AAG in the same patients. Our integrated analysis of transcriptome and methylome revealed DNA hypomethylation in APA and identified several up-regulated genes with DNA hypomethylation that may be involved in aldosterone production and tumorigenesis.
