{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T15:36:47Z","timestamp":1791041807429,"version":"4.1.0"},"reference-count":35,"publisher":"The Endocrine Society","issue":"12","license":[{"start":{"date-parts":[[2020,8,26]],"date-time":"2020-08-26T00:00:00Z","timestamp":1598400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>DNA methylation has been identified among putative regulatory mechanisms for CYP11B2 expression in primary aldosteronism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The objective of this work is to investigate DNA methylation and expression of genes encoding steroidogenic enzymes in benign adrenocortical tumors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design and Setting<\/jats:title>\n                    <jats:p>This cross-sectional study took place at university hospitals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients<\/jats:title>\n                    <jats:p>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).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Intervention<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main Outcome Measure<\/jats:title>\n                    <jats:p>The main outcome measure was DNA methylation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>CYP11B2 methylation levels were significantly lower in APA than in other adrenal tissues (P &amp;lt; .001). Methylation levels of the remaining genes were comparable among groups. Overall, CYP11B2 expression and DNA methylation were negatively correlated (\u03c1 = \u20130.379; P = .003). In FFPE-paired APA\/APCC samples, CYP11B2 methylation level was significantly lower in APA than in concurrent APCCs (P = .028).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgaa585","type":"journal-article","created":{"date-parts":[[2020,8,25]],"date-time":"2020-08-25T21:17:05Z","timestamp":1598390225000},"page":"e4605-e4615","source":"Crossref","is-referenced-by-count":12,"title":["DNA Methylation of Steroidogenic Enzymes in Benign Adrenocortical Tumors: New Insights in Aldosterone-Producing Adenomas"],"prefix":"10.1210","volume":"105","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1291-8906","authenticated-orcid":false,"given":"Guido","family":"Di Dalmazi","sequence":"first","affiliation":[{"name":"Endocrinology and Diabetes Prevention and Care Unit, Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Morandi","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences, Functional MR Unit, IRCCS Istituto delle Scienze Neurologiche di Bologna, Department of Biomedical and Neuromotor Sciences (DIBINEM), Alma Mater Studiorum University of Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Rubin","sequence":"additional","affiliation":[{"name":"Clinica Medica 3, Department of Medicine, University of Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catia","family":"Pilon","sequence":"additional","affiliation":[{"name":"Clinica Medica 3, Department of Medicine, University of Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Asioli","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences, Functional MR Unit, IRCCS Istituto delle Scienze Neurologiche di Bologna, Department of Biomedical and Neuromotor Sciences (DIBINEM), Alma Mater Studiorum University of Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Vicennati","sequence":"additional","affiliation":[{"name":"Endocrinology and Diabetes Prevention and Care Unit, Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"De Leo","sequence":"additional","affiliation":[{"name":"Pathology Unit, S. 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