ECE2019 Guided Posters Adrenal and Neuroendocrine - Basic (14 abstracts)
Identification of genes mediating dysregulated cell growth in aldosterone-producing adenomas
Yuhong Yang 1 , Martina Tetti 2 , Diana Jaquin 1 , Paolo Mulatero 2 , Holger Schneider 1 , Felix Beuschlein 1, , Martin Reincke 1 & Tracy Ann Williams 1,
1Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany; 2Division of Internal Medicine and Hypertension, Department of Medical Sciences, University of Turin, Turin, Italy; 3Klinik für Endokrinologie, Diabetologie und Klinische Ernährung, Universitätsspital Zürich, Zürich, Switzerland.
Background: Aldosterone-producing adenomas (APA) are a major cause of primary aldosteronism. Somatic mutations explain the excess aldosterone production in the majority of patients with APA with mutations in the potassium channel KCNJ5 the most prevalent. In contrast, mechanisms driving cell proliferation are largely unresolved.
Objective: To identify genes that modulate cell growth in APAs.
Methods: Quantitative transcriptome analysis using RNA-seq was used to identify differentially expressed genes between macro-APAs (n=9, diameter ≥30 mm) and micro-APAs (n=12, diameter <10 mm). Validation of RNA-seq by TaqMan real-time PCR was performed for 15 genes in a broader cohort of APAs (wild type, n=28; KCNJ5-mutated, n=43).
Findings: Hierarchical cluster analysis of the top 500 differentially expressed genes indicated sample clustering based on genotype (KCNJ5 or wild type) and APA diameter. Differential expression of 155 and 348 genes was found between micro- and macro-APA with KCNJ5 mutations and wild type, respectively. Several genes were identified with a known function related to cell growth. Expression of BEX1 (a reported tumour suppressor) was 2.8-fold down regulated in macro-APAs relative to micro-APAs (P=0.001), and a linear negative correlation of BEX1 expression with APA diameter was observed in wild type APA (r=−0.501, P=0.007). Genes involved in β-catenin signalling, SFRP2, DKK1 and TSPAN12 were 5.9-fold (P=0.001), 1.8-fold (P=0.038) and 8.3-fold (P<0.0001) down regulated in macro-APAs compared with micro-APAs, respectively.
Interpretation: APA display distinct transcriptome profiles according to adenoma diameter which may help identify genes involved in the dysregulated cell growth associated with these tumours.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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