Characteristics of a Novel ATP2B3 K416_F418delinsN Mutation in a Classical Aldosterone-Producing Adenoma

Abstract

In patients with primary aldosteronism (PA), the prevalence of ATP2B3 mutation is rare. The aim of this study is to report a novel ATP2B3 mutation in a PA patient. Based on our tissue bank of aldosterone-producing adenomas (APA), we identified a novel somatic ATP2B3 K416_F418delinsN mutation. The affected individual was a 53 year-old man with a 4 year history of hypertension. Computed tomography (CT) showed bilateral adrenal masses of 1.6 (left) and 0.5 cm (right) in size. An adrenal venous sampling (AVS) showed a lateralization index (LI) of 2.2 and a contralateral suppression index (CLS) of 0.12; indicating left functional predominance. After a left unilateral adrenalectomy, he achieved partial biochemical and hypertension–remission. This classical adenoma harbored a novel ATP2B3 K416_F418delinsN somatic mutation, which is a deletion from nucleotides 1248 to 1253. The translated amino acid sequence from 416 to 418, reading as lysine-phenylalanine-phenylalanine, was deleted; however, an asparagine was inserted due to merging of residual nucleotide sequences. The CYP11B2 immunohistochemistry staining demonstrated strong immunoreactivity in this classical adenoma. The ATP2B3 K416_F418delinsN mutation is a functional mutation in APA, since HAC15 cells, a human adrenal cell line, transfected with the mutant gene showed increased CYP11B2 expression and aldosterone production.

New Insights in the Genetics and Genomics of Adrenocortical Tumors and Pheochromocytomas

“…The disease phenotype might be associated with some genetic variants, as the article by Chang et al shows greater recovery from arterial stiffness in adenomas harboring KCNJ5 somatic mutations [ 1 ]. The molecular features of a novel mutation in the ATP2B3 gene are presented in detail in the article by Liao et al [ 2 ]. By using advanced bioinformatics approaches, Gong et al characterized the metabolome and tissue microenvironment in aldosterone-producing adenomas and showed metabolic reprogramming toward fatty acid β-oxidation and glycolysis; moreover, an immunosuppressive tissue microenvironment was also found [ 3 ].…”