Endocrine Abstracts

The most frequent molecular alteration in adrenocortical tumors (ACT) is the activation of the Wnt/β-catenin pathway that is associated with poor prognosis in adrenocortical carcinoma. Activating β-catenin mutation (p.S31, p.S37, p.S45, T.41) inhibiting its proteosomal degradation by the canonical destruction complex is responsible for its abnormal activation in roughly 30% of ACT. However, the E3 ubiquitin protein ligase 1, SIAH1 is able to ubiquitinate β-caten...

ARMC5 is a tumor suppressor gene responsible for 20 to 40% of Primary Bilateral Macronodular Adrenal Hyperplasia (PBMAH) with a function that remains unclear. Based on pathway analysis from RNAseq results obtained on zebrafish models of transient Armc5 up- and down-regulation, we identified transcriptional alterations of several members of SIRT1 (sirtuin (silent mating type information regulation 2 homolog) 1) signaling in our models and hypothesized that ARM...

Introduction: Primary Bilateral Macronodular Adrenal Hyperplasia (PBMAH) is a rare cause of ACTH-independent Cushing syndrome. It is characterized by the development of supracentimetric nodules resulting in increased adrenal volume and weight. Its presentation is clinically, radiologically and biologically heterogeneous. Morphological descriptions of PBMAH are rare. Although the initial description highlights that multinodular hyperplastic adrenal glands are made of a majority...

Introduction: Bilateral macronodular adrenal disease (BMAD) is a genetically heterogeneous disease that can be caused by ARMC5 or KDM1A alterations. Indeed, a germline and somatic event leading to a bi-allelic inactivation of ARMC5 or KDM1A are responsible for 20 and 1% of BMAD cases, respectively. Genetic analysis identified three molecular groups: ARMC5, KDM1A and no genetic cause known to date. Although there is a high h...

Adrenocortical carcinoma (ACC) is a rare malignancy with dismal prognosis. Deregulated microRNA (miRNA) expression has been implicated in ACC aggressiveness. Nevertheless, the mechanisms underlying such deregulations remain unknown. Aberrant Wnt/β-Catenin signaling has been reported in about 40% of ACC and is associated with poor outcome. In the present work, we aimed to investigate the link between constitutive activation of Wnt/β-Catenin pathway and miRNA expressio...

Background: Germline mutations of ARMC5 (Armadillo repeat containing 5 gene) were identified as a frequent cause of primary bilateral macronodular adrenal hyperplasia (PBMAH). ARMC5 is considered as a tumor suppressor gene regulating apoptosis and steroidogenesis by unknown mechanisms. The ARMC5 protein contains a N-terminal domain made of Armadillo (ARM) repeats and a C-terminal ‘Bric-a-Brac, Tramtrack, Broad-complex/Pox virus and Zinc finger (BTB/POZ)&...

Introduction: Germline inactivating ARMC5 (Armadillo repeat containing 5) mutations are responsible for Primary Bilateral Macronodular Adrenal Hyperplasia (PBMAH). ARMC5 presents the characteristics of a tumor suppressor gene. Mutations are observed in more than 85% of patients with a clear familial presentation and 20 to 25% of apparently sporadic cases. Genetic alterations are spread all over ARMC5 coding sequence and more than two-third of them ar...

Introduction: Adrenocortical Carcinoma (ACC) is a rare and aggressive tumor with poor prognosis. Up to now, CTNNB1 (βcatenin) and TP53 mutations were the most frequent alterations identified in ACC. By a combination of genomic approaches, we have recently analyzed a cohort of 122 ACC (European Network for the Study of Adrenal Tumors, ENSAT). This work confirmed recurrent alterations in CTNNB1 and TP53 and revealed new genes not previous...

Background: ARMC5 (armadillo repeat containing 5) has been identified as the gene responsible for PBMAH (Primary Bilateral Macronodular Adrenal Hyperplasia). ARMC5 inactivating mutations are reported in 20 to 25% of PBMAH patients. ARMC5, is considered as a tumor suppressor gene controlling apoptosis and regulating steroidogenesis. The mechanisms of action of ARMC5 are unknown. The structure of the ARMC5 protein contains ARM repeats and a BT...

Introduction: ARMC5 germline and somatic inactivating mutations were discovered in patients treated by adrenalectomy for hypercortisolism due to primary bilateral macronodular adrenal hyperplasia (PBMAH). Since then, several ARMC5 germline variants have been described in PBMAH patients. Genetic alterations are spread all over ARMC5 coding sequence and many are missense variants. For them, geneticist conclusions are based on in silico predictions. As ...