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| Status |
Public on May 09, 2015 |
| Title |
Integration of transcriptome and methylome analyses to dissect molecular pathogenesis of primary aldosteronism: comparision between aldosterone-producing adenomas and adjacent adrenal glands [transcriptome] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Primary aldosteronism (PA) is the most common endocrine hypertension comprising 10% of hypertensive patients. A recent series of transcriptome analyses using DNA microarray has shown that neumerous genes are differentially expressed between aldosterone-producing adenoma (APA) and its adjacent adrenal gland (AAG) tissue from the same patient. However, the molecular mechanism(s) of pathogenesis of APA has not yet been fully clarified. Although growing body of evidence has shown that epigenetic abnormalities including DNA methylation play a key role in tumorigenesis, there are few studies with regard to DNA methylation in APA. In the present study, to elucidate the pathogenic relationship between gene expression and DNA methylation in PA, we conducted an integrated analysis of transcriptome and methylome data for paired APA-AAG samples from the same patient. Adrenal specimens were obtained from 7 Japanese patients with APA, who underwent adrenalectomy at Tokyo Medical and Dental University. RNA and DNA samples were extracted from those 7 paired APA and AAG tissues. Gene expression and genome-wide DNA methylation profiles were obtained using SurePrint G3 Human GE 8x60K Microarray (Agilent) and Infinium HumanMethylation450 Beadchip (Illumina), respectively. Transcriptome anlaysis identified 244 significantly (2 fold<) upregulated genes in APA compared to AAG. The upregulated genes include the previously studied genes such as PCP4, ALDH1A2, and CYP11B2, and other genes that have not been previously studied, such as HOXA9, HOXA11, and HOXB9. Gene ontology (GO) analysis for these upregulated genes identified the calcium signaling pathway to be most significantly enriched with the upregulated genes (8 genes). Methylome analysis revealed that APA was globally hypomethylated compared to AAG regardless of gene feature groups, namely, TSS1500, TSS200, 5’UTR, 1stExon, gene body, and 3’UTR. GO analysis for the genes showing hypomethylation at TSS1500/TSS200 regions in APA identified the term “cytokine-cytokine receptor interaction” to be most significantly enriched with hypomethylated genes (37 genes). Integrated analysis of gene expression and genome-wide DNA methylation profiles identified 18 genes that are upregulated and whose TSS1500/TSS200 regions are hypomethylated in APA compared to AAG. These genes include CYP11B2 and MC2R (ACTH receptor). In conclusion, this is the first genome-wide study for PA that integrated transcriptome and methylome data. Global DNA hypomethylation in APA and concordant transcriptional up-regulation of some key genes, such as CYP11B2 and MC2R, may play crucial roles in the pathophysiological significance in PA.
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| Overall design |
Adrenal specimens were obtained from 7 Japanese patients with APA, who underwent adrenalectomy at Tokyo Medical and Dental University. RNA and DNA samples were extracted from those 7 paired APA and AAG tissues. Gene expression and genome-wide DNA methylation profiles were obtained using SurePrint G3 Human GE 8x60K Microarray (Agilent) and Infinium HumanMethylation450 Beadchip (Illumina), respectively.
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| Contributor(s) |
Murakami M, Yoshimoto T, Nakabayashi K, Yoshihiro O |
| Citation(s) |
25953827 |
| Submission date |
Aug 04, 2014 |
| Last update date |
Oct 11, 2016 |
| Contact name |
Kazuhiko Nakabayashi |
| E-mail(s) |
nakabaya-k@ncchd.go.jp
|
| Organization name |
National Research Institute for Child Health and Development
|
| Department |
Department of Maternal-Fetal Biology
|
| Street address |
2-10-1 Okura
|
| City |
Setagaya |
| State/province |
Tokyo |
| ZIP/Postal code |
157-8535 |
| Country |
Japan |
| |
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| Platforms (1) |
| GPL14550 |
Agilent-028004 SurePrint G3 Human GE 8x60K Microarray (Probe Name Version) |
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| Samples (14)
|
| GSM1464109 |
adjacent adrenal gland (AAG) tissue from Case1 |
| GSM1464110 |
aldesterone-producing adenoma (APA) tissue from Case1 |
| GSM1464111 |
adjacent adrenal gland (AAG) tissue from Case2 |
| GSM1464112 |
aldesterone-producing adenoma (APA) tissue from Case2 |
| GSM1464113 |
adjacent adrenal gland (AAG) tissue from Case3 |
| GSM1464114 |
aldesterone-producing adenoma (APA) tissue from Case3 |
| GSM1464115 |
adjacent adrenal gland (AAG) tissue from Case4 |
| GSM1464116 |
aldesterone-producing adenoma (APA) tissue from Case4 |
| GSM1464117 |
adjacent adrenal gland (AAG) tissue from Case5 |
| GSM1464118 |
aldesterone-producing adenoma (APA) tissue from Case5 |
| GSM1464119 |
adjacent adrenal gland (AAG) tissue from Case6 |
| GSM1464120 |
aldesterone-producing adenoma (APA) tissue from Case6 |
| GSM1464121 |
adjacent adrenal gland (AAG) tissue from Case7 |
| GSM1464122 |
aldesterone-producing adenoma (APA) tissue from Case7 |
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| This SubSeries is part of SuperSeries: |
| GSE60044 |
Integration of transcriptome and methylome analyses to dissect molecular pathogenesis of primary aldosteronism: comparision between aldosterone-producing adenomas and adjacent adrenal glands |
|
| Relations |
| BioProject |
PRJNA257370 |
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