We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
DNA Methylation of Steroidogenic Enzymes in Benign Adrenocortical Tumors: New Insights in Aldosterone-Producing Adenomas.
- Authors
Di Dalmazi, Guido; Morandi, Luca; Rubin, Beatrice; Pilon, Catia; Asioli, Sofia; Vicennati, Valentina; De Leo, Antonio; Ambrosi, Francesca; Santini, Donatella; Pagotto, Uberto; Maffeis, Valeria; Fassina, Ambrogio; Fallo, Francesco
- Abstract
<bold>Context: </bold>DNA methylation has been identified among putative regulatory mechanisms for CYP11B2 expression in primary aldosteronism.<bold>Objective: </bold>The objective of this work is to investigate DNA methylation and expression of genes encoding steroidogenic enzymes in benign adrenocortical tumors.<bold>Design and Setting: </bold>This cross-sectional study took place at university hospitals.<bold>Patients: </bold>We collected fresh-frozen tissues from patients with benign adrenocortical adenomas (n = 48) (nonfunctioning n = 9, autonomous cortisol secretion n = 9, Cushing syndrome n = 17, aldosterone-producing [APA] n = 13) and adrenal cortex adjacent to APA (n = 12). We collected formalin-fixed, paraffin-embedded (FFPE) specimens of paired APA and concurrent aldosterone-producing cell clusters (APCCs) (n = 6).<bold>Intervention: </bold>DNA methylation levels were evaluated by quantitative bisulfite next-generation sequencing in fresh-frozen tissues (CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP21A2, HSD3B1, HSD3B2, NR5A1, STAR, and TSPO) and FFPE APA/APCC paired samples (CYP11B2). CYP11B1, CYP11B2, CYP17, CYP21, and STAR gene expressions were examined by quantitative real-time polymerase chain reaction.<bold>Main Outcome Measure: </bold>The main outcome measure was DNA methylation.<bold>Results: </bold>CYP11B2 methylation levels were significantly lower in APA than in other adrenal tissues (P < .001). Methylation levels of the remaining genes were comparable among groups. Overall, CYP11B2 expression and DNA methylation were negatively correlated (ρ = -0.379; P = .003). In FFPE-paired APA/APCC samples, CYP11B2 methylation level was significantly lower in APA than in concurrent APCCs (P = .028).<bold>Conclusions: </bold>DNA methylation plays a regulatory role for CYP11B2 expression and may contribute to aldosterone hypersecretion in APA. Lower CYP11B2 methylation levels in APA than in APCCs may suggest an APCC-to-APA switch via progressive CYP11B2 demethylation. Conversely, DNA methylation seems not to be relevant in regulating the expression of genes encoding steroidogenic enzymes other than CYP11B2.
- Subjects
DNA methylation; BENIGN tumors; MEDICAL sciences; ENZYMES; GENETIC mutation; ENZYME metabolism; RESEARCH; CROSS-sectional method; RESEARCH methodology; METABOLISM; MEDICAL cooperation; EVALUATION research; COMPARATIVE studies; SEX hormones; GENES; ADRENAL tumors; ALDOSTERONE; LONGITUDINAL method
- Publication
Journal of Clinical Endocrinology & Metabolism, 2020, Vol 105, Issue 12, p1
- ISSN
0021-972X
- Publication type
journal article
- DOI
10.1210/clinem/dgaa585