Editors' ChoiceMEDICINE

Candidate Cushing's Culprit Identified

Sci. Signal.  27 May 2014:
Vol. 7, Issue 327, pp. ec142
DOI: 10.1126/scisignal.2005509

Cushing’s syndrome is a rare condition resulting from the excess production of cortisol. About 15% of Cushing’s syndrome cases are associated with an adrenocortical tumor. However, the genetic etiology of these adrenocortical tumors is ill defined (see the Perspective by Kirschner). Cao et al. and Sato et al. both performed whole-exome sequencing of tumors from individuals with adrenal Cushing’s syndrome and compared it with the patient’s own matched nontumor DNA and identified recurrent mutations in the protein kinase A catalytic subunit alpha (PRKACA) gene, as well as less frequent mutations in other putative pathological genes. The most common recurrent mutation activated the kinase, which may suggest a potential therapeutic target.

Y. Cao, M. He, Z. Gao, Y. Peng, Y. Li, L. Li, W. Zhou, X. Li, X. Zhong, Y. Lei, T. Su, H. Wang, Y. Jiang, L. Yang, W. Wei, X. Yang, X. Jiang, L. Liu, J. He, J. Ye, Q. Wei, Y. Li, W. Wang, J. Wang, G. Ning, Activating hotspot L205R mutation in PRKACA and adrenal Cushing’s syndrome. Science 344, 913–917 (2014). [Abstract] [Full Text]

Y. Sato, S. Maekawa, R. Ishii, M. Sanada, T. Morikawa, Y. Shiraishi, K. Yoshida, Y. Nagata, A. Sato-Otsubo, T. Yoshizato, H. Suzuki, Y. Shiozawa, K. Kataoka, A. Kon, K. Aoki, K. Chiba, H. Tanaka, H. Kume, S. Miyano, M. Fukayama, O. Nureki, Y. Homma, S. Ogawa, Recurrent somatic mutations underlie corticotropin-independent Cushing’s syndrome. Science 344, 917–920 (2014). [Abstract] [Full Text]

L. S. Kirschner, A unified cause for adrenal Cushing’s syndrome. Science 344, 804–805 (2014). [Abstract] [Full Text]