title: PRKACA Mutations in Adrenal Adenomas: Genotype/Phenotype Correlations.
abstract: Untargeted, next generation sequencing approaches have provided deep insights into genetic events that result in unopposed steroidogenesis from the adrenal cortex. In particular, somatic mutations in the gene encoding the catalytic subunit α of protein kinase A (PKA) (PRKACA) were identified independently by several groups as the most frequently altered gene in cortisol-producing adenomas. Detailed functional studies could explore the molecular consequences of these hot-spot mutations and large international cohorts have provided the basis to explore the clinical characteristics associated with this mutation. Thereby,PRKACAmutations are highly specific for cortisol over-secretion, while they are absent or very rare in the context of other adrenal diseases. Patients carrying these somatic mutations are affected by a more severe phenotype and are identified at a younger age. Thus, these genotype/phenotype correlations provide further evidence for the importance of PKA-dependent pathways for adrenal physiology and disease.
authors.affiliation: Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, München, Germany.
authors.forename: G D
authors.initials: GD
authors.lastname: Dalmazi
authors.affiliation: Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, München, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Beuschlein
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D018246:Adrenocortical Adenoma / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D000818:Animals; D054751:Cyclic AMP-Dependent Protein Kinase Catalytic Subunits; D006801:Humans; D006854:Hydrocortisone / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D009363:Neoplasm Proteins; D054751:Cyclic AMP-Dependent Protein Kinase Catalytic Subunits; C517757:PRKACA protein, human; D006854:Hydrocortisone