title: GNAS mutations in adrenal aldosterone-producing adenomas.
abstract: Mutations in GNAS, which encodes Gsα, have been documented in detail, particularly in human pituitary GH-secreting adenomas. Mutations have also recently been reported in adrenal cortisol-producing adenomas (CPAs), in addition to those in the PRKACA gene. However, mutations have not yet been examined in aldosterone-producing adenomas (APAs). Therefore, we herein investigated mutations in the GNAS gene in APAs. Two of the 15 (13%) CPAs with overt Cushing's syndrome and one of the 9 (11%) CPAs with subclinical Cushing's syndrome examined had the somatic mutations, p.R201S and p.R201C in the GNAS gene. We identified mutations in the GNAS gene (p.R201C) in 2 out of the 33 (6%) APAs tested, both of which showed autonomous cortisol secretion, while 24 APAs had mutations in the KCNJ5 gene (18 with p.G151R and 6 with p.L168R). These GNAS and KCNJ5 mutations were mutually exclusive in these adenomas. We herein demonstrated for the first time the presence of GNAS mutations in APAs, as well as in some cortisol-secreting adenomas. Our results suggest that these mutations, in addition to mutations in the KCNJ5 gene and other genes such as ATP1A1, ATP2B3 and CACNA1D, may be responsible for the tumorigenesis of APAs and CPAs with subclinical Cushing's syndrome.
authors.affiliation: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.
authors.forename: Yasuyo
authors.initials: Y
authors.lastname: Nakajima
authors.forename: Takashi
authors.initials: T
authors.lastname: Okamura
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Horiguchi
authors.forename: Tamae
authors.initials: T
authors.lastname: Gohko
authors.forename: Tomoko
authors.initials: T
authors.lastname: Miyamoto
authors.forename: Tetsurou
authors.initials: T
authors.lastname: Satoh
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ozawa
authors.forename: Sumiyasu
authors.initials: S
authors.lastname: Ishii
authors.forename: Eijiro
authors.initials: E
authors.lastname: Yamada
authors.forename: Koshi
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Shuichi
authors.initials: S
authors.lastname: Okada
authors.forename: Daisuke
authors.initials: D
authors.lastname: Takata
authors.forename: Jun
authors.initials: J
authors.lastname: Horiguchi
authors.forename: Masanobu
authors.initials: M
authors.lastname: Yamada
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000235:genetics* / Q000378:metabolism; D018246:Adrenocortical Adenoma / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000378:metabolism*; D002864:Chromogranins / Q000235:genetics*; D015331:Cohort Studies; D003480:Cushing Syndrome / Q000235:genetics / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000235:genetics; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D006929:Hyperaldosteronism / Q000235:genetics; D008875:Middle Aged; D009154:Mutation
chemical_list: D002864:Chromogranins; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C484274:KCNJ5 protein, human; D000450:Aldosterone; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs; D006854:Hydrocortisone