ArticleThe Journal of clinical endocrinology and metabolism2016
Molecular Heterogeneity in Aldosterone-Producing Adenomas.
Article in The Journal of clinical endocrinology and metabolism, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 90 citations in OpenAlex.
- Aldosterone-Producing Lesions HarboringHypertension (Dallas, Tex. : 1979) · 2026Article
- CXCR4 reduces aldosterone synthesis via regulating CYP11B2 expression.Genes & diseases · 2026Article
- From bench to bedside: primary aldosteronism revisited.Endocrine connections · 2026Article
- An interpretable machine learning model for preoperative prediction of aldosterone secretion and CYP11B2 status of adrenal gland.BMC medical imaging · 2026Article
- Coexistence of primary aldosteronism and micro-pheochromocytoma: a case report with pathological analysis and literature review.Frontiers in medicine · 2026Article
- Cosyntropin-Stimulated Aldosterone Reserve of the Nondominant Adrenal Predicts Surgical Outcomes in Primary Aldosteronism.Hypertension (Dallas, Tex. : 1979) · 2025Article
- Adrenocortical stem cells in health and disease.Nature reviews. Endocrinology · 2025Review
- Non-canonical Wnt signaling triggered by WNT2B drives adrenal aldosterone production.bioRxiv : the preprint server for biology · 2024Article
- Multifocal, Asymmetric Bilateral Primary Aldosteronism Cannot be Excluded by Strong Adrenal Vein Sampling Lateralization: An International Retrospective Cohort Study.Hypertension (Dallas, Tex. : 1979) · 2024Article
- Double somatic mutations inFrontiers in endocrinology · 2024Article
- Somatic SLC30A1 mutations altering zinc transporter ZnT1 cause aldosterone-producing adenomas and primary aldosteronism.Nature genetics · 2023Article
- CACNA1D-Related Channelopathies: From Hypertension to Autism.Handbook of experimental pharmacology · 2023Review
- Histopathology and Genetic Causes of Primary Aldosteronism in Young Adults.The Journal of clinical endocrinology and metabolism · 2022Article
- Targeted Mutational Analysis of Cortisol-Producing Adenomas.The Journal of clinical endocrinology and metabolism · 2022Article
- Exploration of KCNJ5 Somatic Mutation and CYP11B1/CYP11B2 Staining in Multiple Nodules in Primary Aldosteronism.Frontiers in medicine · 2022Article
- Case Report: Primary Aldosteronism Due to Bilateral Aldosterone-Producing Micronodules With HISTALDO Classical and Contralateral Non-Classical Pathology.Frontiers in endocrinology · 2022Article
- Pathogenesis of Primary Aldosteronism: Impact on Clinical Outcome.Frontiers in endocrinology · 2022Review
- Review
- Article
- Novel Mutations Detection with Next-Generation Sequencing and Its Association with Clinical Outcome in Unilateral Primary Aldosteronism.Biomedicines · 2021Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
contextThe use of next-generation sequencing has resulted in the identification of recurrent somatic mutations underlying primary aldosteronism (PA). However, significant gaps remain in our understanding of the relationship between tumor aldosterone synthase (CYP11B2) expression and somatic mutation status.
objectiveThe objective of the study was to investigate tumor CYP11B2 expression and somatic aldosterone-driver gene mutation heterogeneity.
methodsFifty-one adrenals from 51 PA patients were studied. Immunohistochemistry for CYP11B2 was performed. Aldosterone-producing adenomas with intratumor CYP11B2 heterogeneity were analyzed for mutation status using targeted next-generation sequencing. DNA was isolated from CYP11B2-positive, CYP11B2-negative, and adjacent normal areas from formalin-fixed, paraffin-embedded sections.
resultsOf 51 adrenals, seven (14 %) showed distinct heterogeneity in CYP11B2 by immunohistochemistry, including six adenomas with intratumor heterogeneity and one multinodular hyperplastic adrenal with both CYP11B2-positive and -negative nodules. Of the six adrenocortical adenomas with CYP11B2 heterogeneity, three had aldosterone-regulating mutations (CACNA1D p.F747C, KCNJ5 p.L168R, ATP1A1 p.L104R) only in CYP11B2-positive regions, and one had two different mutations localized to two histologically distinct CYP11B2-positive regions (ATP2B3 p.L424_V425del, KCNJ5 p.G151R). Lastly, one adrenal with multiple CYP11B2-expressing nodules showed different mutations in each (CACNA1D p.F747V and ATP1A1 p.L104R), and no mutations were identified in CYP11B2-negative nodule or adjacent normal adrenal.
conclusionsAdrenal tumors in patients with PA can demonstrate clear heterogeneity in CYP11B2 expression and somatic mutations in driver genes for aldosterone production. These findings suggest that aldosterone-producing adenoma tumorigenesis can occur within preexisting nodules through the acquisition of somatic mutations that drive aldosterone production.
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