Unknown

Dataset Information

0

Aldosterone-Producing Cell Clusters Frequently Harbor Somatic Mutations and Accumulate With Age in Normal Adrenals.


ABSTRACT: Context:Aldosterone synthase (CYP11B2) immunohistochemistry and next-generation sequencing (NGS) have revealed the frequent presence of aldosterone-producing cell clusters (APCCs) harboring somatic mutations in aldosterone-regulating genes in adrenals from Americans without defined hypertension status. Objective:Determine the frequency and somatic mutation status of APCCs in a Japanese nonhypertensive cohort. Design Setting Patients and Interventions:Adrenals from 837 consecutive autopsies at a Japanese institution, Tohoku University Hospital, were screened to select 107 unilateral adrenal glands from nonhypertensive patients. APCC score (APCC number/adrenal cortex area per case) was assessed by CYP11B2 immunohistochemistry. DNA from all APCCs and adjacent adrenal cortex was subjected to NGS using two panels targeting aldosterone-regulating genes. Primary Outcome Measure:APCC frequency and somatic mutation spectrum. Results:In 107 adrenals, 61 APCCs were detected (average of 0.6 APCCs per gland). APCC score was positively correlated with age (r = 0.50, P < 0.0001). NGS demonstrated high confidence somatic mutations in 21 of 61 APCCs (34%). Notably, 16 of 21 APCCs (76%) harbored somatic mutations in CACNA1D, the most frequently mutated gene in our previous studies of APCCs in Americans and CYP11B2-positive micronodules in cross-sectional imaging (computed tomography) negative primary aldosteronism (PA), whereas no APCCs harbored mutations in KCNJ5, the most frequently mutated gene in aldosterone-producing adenoma. APCC score was significantly lower than our previous cohort of unilateral computed tomography-negative PA. Conclusions:APCCs are frequent in nonhypertensive Japanese adrenals, accumulate with age, and frequently harbor somatic mutations (most commonly in CACNA1D). The role of APCCs in PA pathobiology and non-PA hypertension warrants further investigation.

SUBMITTER: Omata K 

PROVIDER: S-EPMC5686701 | BioStudies | 2017-01-01

REPOSITORIES: biostudies

Similar Datasets

2015-01-01 | S-EPMC4547250 | BioStudies
| S-EPMC6207209 | BioStudies
2016-01-01 | S-EPMC5046023 | BioStudies
2019-01-01 | S-EPMC6786771 | BioStudies
2016-01-01 | S-EPMC4803171 | BioStudies
| S-EPMC4474471 | BioStudies
2017-01-01 | S-EPMC5470036 | BioStudies
| S-EPMC4600038 | BioStudies
| S-EPMC5995250 | BioStudies
2019-01-01 | S-EPMC6416065 | BioStudies