title: Novel Insights into the Genetics and Pathophysiology of Adrenocortical Tumors.
abstract: Adrenocortical tumors (ACTs) are typically unilateral and can be classified as benign adrenocortical adenomas (ACAs) or malignant adrenocortical cancers (ACCs). In rare cases, tumors may occur in both adrenal glands as micronodular hyperplasia (primary pigmented nodular adrenal dysplasia) or as macronodular hyperplasia (primary bilateral macronodular adrenal hyperplasia, PBMAH). The study of certain tumor predisposition syndromes has improved our understanding of sporadic ACTs. Most ACAs are associated with abnormalities of the cAMP signaling pathway, whereas most ACCs are linked to alterations in IGF2, TP53, or the Wnt/βcatenin pathways. Over the past year, single-nucleotide polymorphism array technology and next-generation sequencing have identified novel genetic alterations in ACTs that shed new light on the molecular mechanisms of oncogenesis. Among these are somatic mutations of PKA catalytic subunit alpha gene (PRKACA) in ACA, germline, and somatic mutations of armadillo repeat containing 5 gene (ARMC5) in primary bilateral macronodular adrenal hyperplasia and somatic alterations of the E3 ubiquitin ligase gene ZNRF3 in ACC. This review focuses on the recent discoveries and their diagnostic, prognostic, and therapeutic implications.
authors.affiliation: U1016, INSERM, Institut Cochin , Paris , France ; UMR8104, CNRS , Paris , France ; Université Paris Descartes, Sorbonne Paris Cité , Paris , France.
authors.forename: Ludivine
authors.initials: L
authors.lastname: Drougat
authors.affiliation: U1016, INSERM, Institut Cochin , Paris , France ; UMR8104, CNRS , Paris , France ; Université Paris Descartes, Sorbonne Paris Cité , Paris , France.
authors.forename: Hanin
authors.initials: H
authors.lastname: Omeiri
authors.affiliation: U1016, INSERM, Institut Cochin , Paris , France ; UMR8104, CNRS , Paris , France ; Université Paris Descartes, Sorbonne Paris Cité , Paris , France.
authors.forename: Lucile
authors.initials: L
authors.lastname: Lefèvre
authors.affiliation: U1016, INSERM, Institut Cochin , Paris , France ; UMR8104, CNRS , Paris , France ; Université Paris Descartes, Sorbonne Paris Cité , Paris , France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Ragazzon
keywords: ARMC5; PRKACA; ZNRF3; adrenocortical adenoma; adrenocortical carcinoma; hyperplasia