Comprehensive re-sequencing of adrenal aldosterone producing lesions reveal three somatic mutations near the KCNJ5 potassium channel selectivity filter

Tobias Åkerström, Joakim Crona, Alberto Delgado Verdugo, Lee F. Starker, Kenko Cupisti, Holger S. Willenberg, Wolfram T. Knoefel, Wolfgang Saeger, Alfred Feller, Julian Ip, Patsy Soon, Martin Anlauf, Pier F. Alesina, Kurt W. Schmid, Myriam Decaussin, Pierre Levillain, Bo Wängberg, Jean Louis Peix, Bruce Robinson, Jan ZedeniusMartin Bäckdahl, Stefano Caramuta, K. Alexander Iwen, Johan Botling, Peter Stålberg, Jean Louis Kraimps, Henning Dralle, Per Hellman, Stan Sidhu, Gunnar Westin, Hendrik Lehnert, Martin K. Walz, Göran Åkerström, Tobias Carling, Murim Choi, Richard P. Lifton, Peyman Björklund*

*Corresponding author for this work
93 Citations (Scopus)


Background: Aldosterone producing lesions are a common cause of hypertension, but genetic alterations for tumorigenesis have been unclear. Recently, either of two recurrent somatic missense mutations (G151R or L168R) was found in the potassium channel KCNJ5 gene in aldosterone producing adenomas. These mutations alter the channel selectivity filter and result in Na+ conductance and cell depolarization, stimulating aldosterone production and cell proliferation. Because a similar mutation occurs in a Mendelian form of primary aldosteronism, these mutations appear to be sufficient for cell proliferation and aldosterone production. The prevalence and spectrum of KCNJ5 mutations in different entities of adrenocortical lesions remain to be defined. Materials and Methods: The coding region and flanking intronic segments of KCNJ5 were subjected to Sanger DNA sequencing in 351 aldosterone producing lesions, from patients with primary aldosteronism and 130 other adrenocortical lesions. The specimens had been collected from 10 different worldwide referral centers. Results: G151R or L168R somatic mutations were identified in 47% of aldosterone producing adenomas, each with similar frequency. A previously unreported somatic mutation near the selectivity filter, E145Q, was observed twice. Somatic G151R or L168R mutations were also found in 40% of aldosterone producing adenomas associated with marked hyperplasia, but not in specimens with merely unilateral hyperplasia. Mutations were absent in 130 non-aldosterone secreting lesions. KCNJ5 mutations were overrepresented in aldosterone producing adenomas from female compared to male patients (63 vs. 24%). Males with KCNJ5 mutations were significantly younger than those without (45 vs. 54, respectively; p<0.005) and their APAs with KCNJ5 mutations were larger than those without (27.1 mm vs. 17.1 mm; p<0.005). Discussion: Either of two somatic KCNJ5 mutations are highly prevalent and specific for aldosterone producing lesions. These findings provide new insight into the pathogenesis of primary aldosteronism.

Original languageEnglish
Article numbere41926
JournalPLoS ONE
Issue number7
Publication statusPublished - 27.07.2012


Dive into the research topics of 'Comprehensive re-sequencing of adrenal aldosterone producing lesions reveal three somatic mutations near the KCNJ5 potassium channel selectivity filter'. Together they form a unique fingerprint.

Cite this