Aldosterone-producing cell clusters frequently harbor somatic mutations and accumulate with age in normal adrenals

Kei Omata, Sharath K. Anand, Daniel H. Hovelson, Chia Jen Liu, Yuto Yamazaki, Yasuhiro Nakamura, Sadayoshi Ito, Fumitoshi Satoh, Hironobu Sasano, William E. Rainey, Scott A. Tomlins

研究成果: Article査読

47 被引用数 (Scopus)


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.DNAfrom 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.

ジャーナルJournal of the Endocrine Society
出版ステータスPublished - 2017 7

ASJC Scopus subject areas

  • 内分泌学、糖尿病および代謝内科学


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