Double-Trouble Mutation

Science Signaling  15 Feb 2011:
Vol. 4, Issue 160, pp. ec47
DOI: 10.1126/scisignal.4160ec47

Many endocrine tumors do not metastasize but, nonetheless, can adversely affect health because the tumor cells secrete excessive amounts of hormones. Aldosterone-producing adrenal adenomas (APAs), for example, can cause severe hypertension. The molecular mechanism coupling uncontrolled cell proliferation with hormone production in these tumors has been unclear. Using an exome-sequencing approach to identify faulty genes in human APAs, Choi et al. (see the Perspective by Funder) found that about one-third of the tumors examined had somatic mutations in the gene encoding the KCNJ5 potassium channel. The mutations allowed inappropriate permeation of sodium into the channel, resulting in cell depolarization. Because cell depolarization in the adrenal cortex is a signal for both aldosterone production and cell growth, disruption of this potassium channel explains the two prominent features of this kind of tumor.

M. Choi, U. I. Scholl, P. Yue, P. Björklund, B. Zhao, C. Nelson-Williams, W. Ji, Y. Cho, A. Patel, C. J. Men, E. Lolis, M. V. Wisgerhof, D. S. Geller, S. Mane, P. Hellman, G. Westin, G. Åkerström, W. Wang, T. Carling, R. P. Lifton, K+ channel mutations in adrenal aldosterone-producing adenomas and hereditary hypertension. Science 331, 768–772 (2011). [Abstract] [Full Text]

J. W. Funder, The genetics of primary aldosteronism. Science 331, 685–686 (2011). [Abstract] [Full Text]