ArticleNature genetics2014
Recurrent activating mutation in PRKACA in cortisol-producing adrenal tumors.
Article in Nature genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 116 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
116 citing papers in PubMed, 1 synthesis or guideline pooled it, 242 citations in OpenAlex.
- Adrenal mixed corticomedullary tumors: report of a case with molecular characterization and systematic review.Virchows Archiv : an international journal of pathology · 2026Pooled it
- The βBritish journal of pharmacology · 2026Article
- Molecular pathology of primary aldosteronism and hypercortisolism: Impact on adrenal surgery.iScience · 2026Review
- Adrenal histologic and genetic characteristics of primary aldosteronism in late adulthood.European journal of endocrinology · 2026Article
- Recent progress in pathophysiology of cortisol-producing adrenal tumor.Endocrine journal · 2026Review
- cAMP/PKA signaling in endocrine hypertension: genetic mechanisms and pathophysiological insights.Frontiers in endocrinology · 2026Review
- Review
- Adrenocortical stem cells in health and disease.Nature reviews. Endocrinology · 2025Review
- 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
- Molecular characterization of archival adrenal tumor tissue from patients with ACTH-independent Cushing syndrome.The Journal of steroid biochemistry and molecular biology · 2025Review
- Characterisation of aEndocrine oncology (Bristol, England) · 2025Article
- The molecular genetics of adrenal cushing.Hormones (Athens, Greece) · 2024Review
- Molecular and Genetics Perspectives on Primary Adrenocortical Hyperfunction Disorders.International journal of molecular sciences · 2024Review
- Therapeutic, Clinicopathological, and Molecular Correlates ofPharmaceuticals (Basel, Switzerland) · 2024Article
- Steroids-producing nodules: a two-layered adrenocortical nodular structure as a precursor lesion of cortisol-producing adenoma.EBioMedicine · 2024Article
- 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
- The effects of 20-hydroxyecdysone on nuclear shape, heterochromatin quantity and gray-level co-occurrence matrix texture analysis of adrenal zona fasciculata cells in an obese gerbil (Gerbillus tarabuli) model for metabolic syndrome: a correlational study.Histochemistry and cell biology · 2023Article
56 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issuedKuntsman, John W [corrected to Kunstman, John W]
Authors and funding
19 authors at 6 institutions in 3 countries.
Funding
Abstract
Adrenal tumors autonomously producing cortisol cause Cushing's syndrome. We performed exome sequencing of 25 tumor-normal pairs and identified 2 subgroups. Eight tumors (including three carcinomas) had many somatic copy number variants (CNVs) with frequent deletion of CDC42 and CDKN2A, amplification of 5q31.2 and protein-altering mutations in TP53 and RB1. Seventeen tumors (all adenomas) had no somatic CNVs or TP53 or RB1 mutations. Six of these had known gain-of-function mutations in CTNNB1 (β-catenin) or GNAS (Gαs). Six others had somatic mutations in PRKACA (protein kinase A (PKA) catalytic subunit) resulting in a p.Leu206Arg substitution. Further sequencing identified this mutation in 13 of 63 tumors (35% of adenomas with overt Cushing's syndrome). PRKACA, GNAS and CTNNB1 mutations were mutually exclusive. Leu206 directly interacts with the regulatory subunit of PKA, PRKAR1A. Leu206Arg PRKACA loses PRKAR1A binding, increasing the phosphorylation of downstream targets. PKA activity induces cortisol production and cell proliferation, providing a mechanism for tumor development. These findings define distinct mechanisms underlying adrenal cortisol-producing tumors.
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What OpenQuestion holds
Registered trials
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.