Aldosterone-Producing Cell Clusters (APCC) Frequently Harbor Somatic Mutations and Accumulate with Age in Normal Adrenals

Presentation Number: OR10-2
Date of Presentation: April 3rd, 2017

Kei Omata*1, Sharath Anand2, Daniel H Hovelson1, Chia-Jen Liu2, Yuto Yamazaki3, Yasuhiro Nakamura4, Fumitoshi Satoh3, Sadayoshi Ito5, Hironobu Sasano3, William E. Rainey1 and Scott A Tomlins1
1University of Michigan, Ann Arbor, MI, 2University of Michigan, 3Tohoku University Graduate School of Medicine, Sendai, Japan, 4Tohoku Medical and Pharmaceutical University, Sendai, Japan, 5Tohoku University Hospital, Sendai, Japan


Context. Aldosterone synthase (CYP11B2) immunohistochemistry and next generation sequencing (NGS) have revealed the frequent presence of aldosterone-producing cells clusters (APCC) harboring somatic mutations in aldosterone regulating genes in adrenal glands from Caucasian patients without defined hypertension status.

Objective. Determine the frequency and somatic mutation status of APCCs in a large cohort of non-hypertensive cases from Japanese subjects.

Method. From 837 consecutive autopsies at a single Japanese institution, unilateral adrenal glands of 107 non-hypertensive patients were retrieved. 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 to identify somatic mutations.

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 driving somatic mutations in 21 of 61 APCCs (34%). Of particular interest, 66% (14/21) of the somatic mutations were in CACNA1D, the most frequently mutated gene in our previous study of Caucasian APCCs, whereas no mutations were identified in KCNJ5, the most frequently mutated gene in aldosterone producing adenomas (APAs).

Conclusions. APCCs are frequent in a large cohort of non-hypertensive Japanese cases, accumulate with age, and frequently harbor somatic mutations (most commonly in CACNA1D). The role of APCCs in primary aldosteronism pathobiology and hypertension warrants further investigation.


Disclosure: SAT: Speaker, Thermo Fisher Scientific, Principal Investigator, Thermo Fisher Scientific. Nothing to Disclose: KO, SA, DHH, CJL, YY, YN, FS, SI, HS, WER