Constitutive activation of PKA catalytic subunit in adrenal Cushing's syndrome.

ABSTRACT:

Background

Corticotropin-independent Cushing's syndrome is caused by tumors or hyperplasia of the adrenal cortex. The molecular pathogenesis of cortisol-producing adrenal adenomas is not well understood.

Methods

We performed exome sequencing of tumor-tissue specimens from 10 patients with cortisol-producing adrenal adenomas and evaluated recurrent mutations in candidate genes in an additional 171 patients with adrenocortical tumors. We also performed genomewide copy-number analysis in 35 patients with cortisol-secreting bilateral adrenal hyperplasias. We studied the effects of these genetic defects both clinically and in vitro.

Results

Exome sequencing revealed somatic mutations in PRKACA, which encodes the catalytic subunit of cyclic AMP-dependent protein kinase (pro

SUBMITTER: Beuschlein F 

PROVIDER: S-EPMC4727447 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature