ArticleThe Journal of clinical endocrinology and metabolism2014
Novel somatic mutations in the catalytic subunit of the protein kinase A as a cause of adrenal Cushing's syndrome: a European multicentric study.
Article in The Journal of clinical endocrinology and metabolism, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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60 citing papers in PubMed, 112 citations in OpenAlex.
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- Molecular characterization of archival adrenal tumor tissue from patients with ACTH-independent Cushing syndrome.The Journal of steroid biochemistry and molecular biology · 2025Review
- The mutational landscape of ARMC5 in Primary Bilateral Macronodular Adrenal Hyperplasia: an update.Orphanet journal of rare diseases · 2025Review
- Germline targeted next-generation sequencing in patients with adrenal incidentalomas.Frontiers in endocrinology · 2025Article
- Characterisation of aEndocrine oncology (Bristol, England) · 2025Article
- Protein kinase A and local signaling in cancer.The Biochemical journal · 2024Review
- Therapeutic, Clinicopathological, and Molecular Correlates ofPharmaceuticals (Basel, Switzerland) · 2024Article
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- Protein Kinase A in neurological disorders.Journal of neurodevelopmental disorders · 2024Review
- Discovery of a Cushing's syndrome protein kinase A mutant that biases signaling through type I AKAPs.Science advances · 2024Article
- Molecular pathology of endocrine gland tumors: genetic alterations and clinicopathologic relevance.Virchows Archiv : an international journal of pathology · 2024Review
- Germline PRKACA amplification-associated primary pigmented nodular adrenocortical disease: a case report and literature review.Archives of endocrinology and metabolism · 2023Review
- Classification of Cushing's syndrome PKAc mutants based upon their ability to bind PKI.The Biochemical journal · 2023Article
- Hereditary Endocrine Tumor Registries.Journal of the Endocrine Society · 2023Article
- Evaluation of Protein Kinase cAMP-Activated Catalytic Subunit Alpha as a Therapeutic Target for Fibrolamellar Carcinoma.Gastro hep advances · 2023Article
- Mislocalization of protein kinase A drives pathology in Cushing's syndrome.Cell reports · 2022Article
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Authors and funding
20 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
contextSomatic mutations in PRKACA gene, encoding the catalytic subunit of protein kinase A (PKA), have been recently found in a high proportion of sporadic adenomas associated with Cushing's syndrome. The aim was to analyze the PRKACA mutation in a large cohort of patients with adrenocortical masses.
methodsSamples from nine European centers were included (Germany, n = 4; Italy, n = 4; France, n = 1). Samples were drawn from 149 patients with nonsecreting adenomas (n = 32 + 2 peritumoral), subclinical hypercortisolism (n = 36), Cushing's syndrome (n = 64 + 2 peritumoral), androgen-producing tumors (n = 4), adrenocortical carcinomas (n = 5 + 2 peritumoral), and primary bilateral macronodular adrenal hyperplasias (n = 8). Blood samples were available from patients with nonsecreting adenomas (n = 15), subclinical hypercortisolism (n = 10), and Cushing's syndrome (n = 35). Clinical and hormonal data were collected. DNA amplification by PCR of exons 6 and 7 of the PRKACA gene and direct sequencing were performed.
resultsPRKACA heterozygous mutations were found in 22/64 samples of Cushing's syndrome patients (34%). No mutations were found in peritumoral tissue and blood samples or in other tumors examined. The c.617A>C (p.Leu206Arg) occurred in 18/22 patients. Furthermore, two novel mutations were identified: c.600_601insGTG/p.Cys200_Gly201insVal in three patients and c.639C>G+c.638_640insATTATCCTGAGG/p.Ser213Arg+p.Leu212_Lys214insIle-Ile-Leu-Arg) in one. All the mutations involved a region implicated in interaction between PKA regulatory and catalytic subunits. Patients with somatic PRKACA mutations showed higher levels of cortisol after dexamethasone test and a smaller adenoma size, compared with nonmutated subjects.
conclusionsThese data confirm and extend previous observations that somatic PRKACA mutations are specific for adrenocortical adenomas causing Cushing's syndrome.
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