ESPEYB18 8. Adrenals New Paradigms (2 abstracts)
8.14. DNA Methylation of steroidogenic enzymes in benign adrenocortical tumors: New insights in aldosterone-producing Adenomas
Di Dalmazi G , Morandi L , Rubin B , Pilon C , Asioli S , Vicennati V , De Leo A , Ambrosi F , Santini D , Pagotto U , Maffeis V , Fassina A & Fallo F
J Clin Endocrinol Metab. 2020 Dec 1;105(12): dgaa585.https://pubmed.ncbi.nlm.nih.gov/32844182/
The aim of this histological study was to investigate DNA methylation and expression of genes encoding steroidogenic enzymes in benign adrenocortical tumors. The findings suggest that DNA methylation plays a regulatory role in CYP11B2 expression and may contribute to aldosterone hypersecretion in aldosterone-producing adrenocortical adenomas (APA).
DNA methylation of CpG islands in promoter and non-promoter regions is one of the most studied heritable regulatory mechanisms and has been recognized in regulatory process of expression of genes involved in tumorigenesis. This cross sectional study examined DNA methylation in fresh-frozen tissues from patients with benign adrenocortical adenomas (n=48) and compared its sub-types (non-functioning, n=9; autonomous cortisol secretion, n=9; Cushing syndrome, n=17; aldosterone-producing [APA], n=13; adrenal cortex adjacent to APA, n=12). The authors performed targeted analysis of methylation of steroidogenic enzymes in benign adrenocortical tumors according to their functional status.
CYP11B2 methylation levels were lower in APA than in other adrenal tissues. Methylation levels of remaining genes were comparable among groups. Overall, CYP11B2 expression and DNA methylation were negatively correlated. In FFPE paired APA/APCC samples, CYP11B2 methylation level was lower in APA than in concurrent APCCs. 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.
Volume 18
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ESPE Yearbook of Paediatric Endocrinology
ISSN 1662-4009 (Online)
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