What question did this study set out to answer?

To investigate the genetic spectrum of aldosterone-producing adenomas and nodules in a Brazilian cohort and identify somatic drivers related to primary aldosteronism.

January 10, 2026

Somatic drivers in aldosterone-producing adenomas and nodules: Insights from a Brazilian cohort of primary aldosteronism

Q: What does this research mean for the field?

ATP2B3 mutations occur in 11.29% of aldosterone-producing adenomas in a Brazilian cohort, significantly higher than the 4.06% seen in other ethnicities. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.CHALLENGES_CONSENSUS.

Key Result

In a Brazilian cohort, ATP2B3 mutations occurred in 11.29% of aldosterone-producing adenomas, significantly higher than the 4.06% seen in other ethnicities (p=0.0053).

Key Points

To investigate the genetic spectrum of aldosterone-producing adenomas and nodules in a Brazilian cohort and identify somatic drivers related to primary aldosteronism.
Analyzed 62 lesions from 61 patients with primary aldosteronism and classical histology.
Used CYP11B2 immunostaining to identify lesions before extracting somatic DNA.
Conducted Sanger sequencing on hotspot regions and performed whole-exome sequencing on cases without known driver variants.
Identified somatic pathogenic variants in 82.26% of lesions, with KCNJ5 being the most common (56.45%).
Detected a significantly higher frequency of ATP2B3 variants at 11.29%, compared to 4.06% in other ethnic cohorts (p=0.0053).
Found nine novel variants, including multiple mutations across ATP2B3, KCNJ5, CACNA1D, and CTNNB1.

Structured PICO

What is the genetic spectrum of somatic drivers in aldosterone-producing adenomas and nodules in a Brazilian cohort with primary aldosteronism?

Population

61 consecutive patients (median age 49 years, 59% women) with primary aldosteronism and classical histology (62 lesions including aldosterone-producing adenomas and nodules) from a Brazilian cohort.

Intervention

Sanger sequencing of hotspot regions (KCNJ5, ATP1A1, ATP2B3, CACNA1D, CTNNB1) and whole-exome sequencing of paired somatic and germline DNA.

Outcome

Genetic spectrum and frequency of somatic driver variants in aldosterone-producing adenomas and nodules.

This study identifies a uniquely high frequency of ATP2B3 somatic variants in a Brazilian cohort with primary aldosteronism, highlighting the impact of population-specific genetic backgrounds on the disease.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

Abstract Background The Brazilian population represents a mosaic of genetic diversity resulting from admixture ancestries. Given reported disparities in primary aldosteronism (PA) genetics across ethnicities, we investigated the genetic spectrum of aldosterone-producing adenomas (APAs) and nodules (APNs) with classical histology in a Brazilian cohort. Methods We included 62 lesions (one case with bilateral APAs) from 61 consecutive patients (median age at PA diagnosis 49 years, 59% women) with PA and classical histology, defined by CYP11B2 immunostaining (HISTALDO consensus). Somatic DNA was extracted from CYP11B2-positive areas of the dominant lesions. Hotspot regions of KCNJ5, ATP1A1, ATP2B3, CACNA1D, and CTNNB1 were initially analyzed by Sanger sequencing. Whole-exome sequencing (WES) of paired somatic and germline DNA was subsequently performed in cases without driver variants. Results Histopathology showed combined APA + aldosterone-producing micronodules as the most frequent subtype (n=29, 47.54%), followed by isolated APA (n=20, 32.79%) and APN (n=5, 8.2%). Somatic PVs were identified in 82.26% of lesions: KCNJ5 (n=35, 56.45%), ATP2B3 (n=7, 11.29%), CACNA1D (n=5, 8.06%) and ATP1A1 (n=4, 6.45%). Nine novel variants were identified, including three in ATP2B3 (two exon 8 in-frame deletions and one missense), three in KCNJ5, two in CACNA1D, and one in CTNNB1. The frequency of ATP2B3 variants (11.29%) was significantly higher than that reported in other cohorts (4.06%) from different ethnicities (p=0.0053). ATP2B3-mutated tumors occurred predominantly in older men and were smaller in size compared with wild-type tumors. Rare germline CACNA1H variants were also detected in three patients. Conclusion We confirmed the predominance of known somatic drivers and identified a uniquely high frequency of ATP2B3 variants, refining their clinical phenotype. These findings underscore the influence of population-specific genetic backgrounds and expand the global understanding of PA genetics.

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