ArticleThe New England journal of medicine2014
Constitutive activation of PKA catalytic subunit in adrenal Cushing's syndrome.
Article in The New England journal of medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00669266 (Investigation of the Tumorigenesis of Adrenal Tumors and Evaluation of New Therapeutic Options - Untersuchungen Zur Tumorgenese Von Nebennierentumoren Und Evaluation Neuer Therapieoptionen), which is not on this map. Cited by 206 papers.
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Investigation of the Tumorigenesis of Adrenal Tumors and Evaluation of New Therapeutic Options - Untersuchungen Zur Tumorgenese Von Nebennierentumoren Und Evaluation Neuer Therapieoptionen
Who cites it
206 citing papers in PubMed, 427 citations in OpenAlex.
- Phosphoproteomic dysregulation promotes tumor proliferation in Cushing's disease.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The identification of a PRKACA duplication at 19p13.12 in a female with PPNAD and thyroid carcinoma after a 20-year diagnostic journey.Familial cancer · 2026Article
- The βBritish journal of pharmacology · 2026Article
- Molecular pathology of primary aldosteronism and hypercortisolism: Impact on adrenal surgery.iScience · 2026Review
- The genetics of hypertension.Nature reviews. Nephrology · 2026Review
- Recent progress in pathophysiology of cortisol-producing adrenal tumor.Endocrine journal · 2026Review
- Case Report: a family presenting with β-adrenergic/vasopressin-responsive bilateral macronodular adrenal disease with anFrontiers in endocrinology · 2026Article
- cAMP/PKA signaling in endocrine hypertension: genetic mechanisms and pathophysiological insights.Frontiers in endocrinology · 2026Review
- Review
- Comparative Proteomic Profiling of Adrenocortical Neoplasia Using Mass Spectrometry.Journal of proteome research · 2025Article
- Article
- A Bibliometric Analysis and Visualization of the Current Status and Future Perspectives of Adrenal Cortical Adenoma.Cureus · 2025Review
- Protein kinase A: a quirky prototype.The FEBS journal · 2025Article
- Genome-wide RNAi screening in C. elegans reveals OXPHOS and pyrimidine synthesis pathways as PKA regulators.Communications biology · 2025Article
- Hedgehog pathway, cell cycle, and primary cilium.Cell death discovery · 2025Review
- Review
- A lipid metabolism related gene signature predicts postoperative recurrence in pancreatic cancer through multicenter cohort validation.Scientific reports · 2025Article
- A Rare Case ofJCEM case reports · 2025Article
- Molecular characterization of archival adrenal tumor tissue from patients with ACTH-independent Cushing syndrome.The Journal of steroid biochemistry and molecular biology · 2025Review
- The Spectrum of GH Excess in Carney Complex and Genotype-phenotype Correlations.The Journal of clinical endocrinology and metabolism · 2025Article
146 more citing papers are in PubMed but not listed here.
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Authors and funding
30 authors at 7 institutions in 9 countries.
Funding
Abstract
backgroundCorticotropin-independent Cushing's syndrome is caused by tumors or hyperplasia of the adrenal cortex. The molecular pathogenesis of cortisol-producing adrenal adenomas is not well understood.
methodsWe performed exome sequencing of tumor-tissue specimens from 10 patients with cortisol-producing adrenal adenomas and evaluated recurrent mutations in candidate genes in an additional 171 patients with adrenocortical tumors. We also performed genomewide copy-number analysis in 35 patients with cortisol-secreting bilateral adrenal hyperplasias. We studied the effects of these genetic defects both clinically and in vitro.
resultsExome sequencing revealed somatic mutations in PRKACA, which encodes the catalytic subunit of cyclic AMP-dependent protein kinase (protein kinase A [PKA]), in 8 of 10 adenomas (c.617A→C in 7 and c.595_596insCAC in 1). Overall, PRKACA somatic mutations were identified in 22 of 59 unilateral adenomas (37%) from patients with overt Cushing's syndrome; these mutations were not detectable in 40 patients with subclinical hypercortisolism or in 82 patients with other adrenal tumors. Among 35 patients with cortisol-producing hyperplasias, 5 (including 2 first-degree relatives) carried a germline copy-number gain (duplication) of the genomic region on chromosome 19 that includes PRKACA. In vitro studies showed impaired inhibition of both PKA catalytic subunit mutants by the PKA regulatory subunit, whereas cells from patients with germline chromosomal gains showed increased protein levels of the PKA catalytic subunit; in both instances, basal PKA activity was increased.
conclusionsGenetic alterations of the catalytic subunit of PKA were found to be associated with human disease. Germline duplications of this gene resulted in bilateral adrenal hyperplasias, whereas somatic PRKACA mutations resulted in unilateral cortisol-producing adrenal adenomas. (Funded by the European Commission Seventh Framework Program and others.).
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.