Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA356253 | ENA |
REPOSITORIES: ENA
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Project description:Analysis of aldosterone-producing adenoma (APA) samples from patients with primary hyperaldosteronism. These APAs have a somatic mutation in either KCNJ5, CACNA1D, or ATP1A1. Results provide insight into the different mechanisms each mutation may cause leading to elevated aldosterone production in APA. In this dataset, we include expression data from aldosterone-producing adenomas (APAs) with a somatic mutation in either KCNJ5, CACNA1D, or ATP1A1. These data are used to obtain differentially expressed genes between KCNJ5 mutant APAs and CACNA1D/ATP1A1 mutant APAs.
2013-07-14 | GSE48303 | GEO
Project description: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.
2018-01-08 | GSE90867 | GEO
Project description:Analysis of aldosterone-producing adenoma (APA) samples from patients with primary hyperaldosteronism. These APAs have a somatic mutation in either KCNJ5, CACNA1D, or ATP1A1. Results provide insight into the different mechanisms each mutation may cause leading to elevated aldosterone production in APA. In this dataset, we include expression data from aldosterone-producing adenomas (APAs) with a somatic mutation in either KCNJ5, CACNA1D, or ATP1A1. These data are used to obtain differentially expressed genes between KCNJ5 mutant APAs and CACNA1D/ATP1A1 mutant APAs. A total of 13 samples were analyzed (8 KCNJ5 mutant APAs and 5 CACNA1D/ATP1A1 mutant APAs). 43 genes had a false discovery rate (FDR) <0.5% and were >2-fold different between KCNJ5 mutant APAs and 5 CACNA1D/ATP1A1 mutant APAs. The two sets of genotypes were separated on unsupervised hierarchical clustering of 1475 genes correlating >0.6 with CYP11B2.
2013-07-14 | E-GEOD-48303 | biostudies-arrayexpress
Project description:Expression data from aldosterone-producing adenomas (APAs) with a somatic mutation in either KCNJ5, CACNA1D, or ATP1A1
| PRJNA209630 | ENA
Project description:Primary aldosteronism is frequently caused by an adrenocortical aldosterone-producing adenoma (APA) carrying a somatic mutation that drives aldosterone overproduction. APAs with a mutation in KCNJ5 (APA-KCNJ5MUT) are characterized by heterogeneous CYP11B2 (aldosterone synthase) expression, a particular cellular composition and larger tumor diameter than those with wild-type KCNJ5 (APA-KCNJ5WT). Here, we used spatial transcriptomics profiling of adrenal tissue cryosections to define the role of transcriptomic reprogramming in APA pathophysiology. Our findings advance the understanding of the transcriptional context of inter- and intra-tumoral APA heterogeneity and provide novel insight into the genotype-dependent tumor expansion capabilities of APAs.
2024-08-13 | GSE274314 | GEO
Project description:Background. Primary aldosteronism is the most common form of secondary hypertension. The most frequent genetic cause of aldosterone producing adenoma (APA) are somatic mutations in the potassium channel KCNJ5. They affect the ion selectivity of the channel, with sodium influx leading to cell membrane depolarization and activation of calcium signalling, the major trigger for aldosterone biosynthesis. Methods. To investigate how KCNJ5 mutations lead to the development of APA, we established an adrenocortical cell model in which sodium entry into the cells can be modulated “on demand” using chemogenetic tools (H295R-S2 α7-5HT3 cells). We investigated their functional and molecular characteristics with regard to aldosterone biosynthesis and cell proliferation. Results. A clonal cell line with stable expression of the chimeric α7-5HT3 receptor in H295R-S2 cells was obtained. Increased sodium entry through the α7-5HT3 receptor upon stimulation with uPSEM-817 led to cell membrane depolarization, opening of voltage-gated Ca2+ channels and increased intracellular Ca2+ concentrations, resulting in the stimulation of CYP11B2 expression and increased aldosterone biosynthesis. Increased intracellular sodium influx did not increase proliferation, but rather induced apoptosis. RNA sequencing and steroidome analyses revealed unique profiles associated with Na+ entry, with only partial overlap with angiotensin II or potassium induced changes. Conclusion. H295R-S2 α7-5HT3 cells are a new model reproducing the major features of cells harbouring KCNJ5 mutations. Increased expression of CYP11B2 and stimulation of the mineralocorticoid biosynthesis pathway are associated with a decrease of cell proliferation and an increase of apoptosis, indicating that additional events may be required for the development of APA.
2025-01-19 | GSE282358 | GEO
Project description:Learn about the transcriptome profiling of zona glomerulosa (ZG), zona fasciculata (ZF) and aldosterone-producing adenomas (APA) in human adrenals
2015-09-15 | GSE64957 | GEO
Project description:Learn about the transcriptome profiling of zona glomerulosa (ZG), zona fasciculata (ZF) and aldosterone-producing adenomas (APA) in human adrenals 21 pairs of zona fasciculata (ZF) and zona glomerulosa (ZG), and 14 paired aldosterone-producing adenomas (APAs) from 14 Conn’s syndrome patients and 7 phaeochromocytoma patients were assayed on the Affymetrix Human Genome U133 Plus 2.0 Array. Laser capture microdissection was used to acquire samples of ZF, ZG and APA as previously described (Azizan EA, et al. J Clin Endocrinol Metab. 2012;97:E819-E829). For differentiation of ZG from ZF, sections were stained with cresyl violet using the LCM Staining Kit (AM1935, Ambion, USA). Data processing and analysis was performed using AffymetrixGeneChip Command Console Software and PartekGenomicSuite 6.5 (Partek Inc., St. Louis, MO). Gene expressions were portrayed as the summarized log-signal of the Robust Multichip Average (RMA) with quantilenormalisation and median polish for probe set summarisation. Validation by qPCR was performed on genes >10 fold up-regulated in zona glomerulosa (compared to zona fasciculata) and >10 fold up-regulated in aldosterone-producing adenomas (compared to zona glomerulosa).
2015-09-15 | E-GEOD-64957 | biostudies-arrayexpress
Project description:Microarray study of human adrenal zona glomerulosa (ZG), zona fasciculata (ZF) and aldosterone-producing adenomas (APA)
| PRJNA272584 | ENA