title: Somatic mutations of the catalytic subunit of cyclic AMP-dependent protein kinase (PRKACA) gene in Japanese patients with several adrenal adenomas secreting cortisol [Rapid Communication].
abstract: Somatic mutations of the catalytic subunit of the cyclic AMP-dependent protein kinase (PRKACA) gene have recently been identified in about 35% of cortisol-producing adenomas (CPAs), with the affected patients showing overt Cushing's syndrome. Since we recently reported higher prevalence of mutations of the KCNJ5 gene and associations with autonomous cortisol secretion in Japanese aldosterone-producing adenomas than in Western countries, there might be different features of CPAs between Japan and the West. We therefore investigated mutations of the PRKACA gene in Japanese patients with several adrenal tumors secreting cortisol, including overt Cushing's syndrome, subclinical Cushing's syndrome, and aldosterone-producing adenomas (APAs) co-secreting cortisol operated on at Gunma University Hospital. Of the 13 patients with CPA who showed overt Cushing's syndrome, 3 (23%) had recurrent somatic mutations of the PRKACA gene, p.L206R (c.617 T>G), and there were no mutations in subclinical Cushing's syndrome. Among 33 APAs, 24 had somatic mutations of the KCNJ5 gene, either G151R or L168R, 11 (33%) had autonomous cortisol secretion, but there were no mutations of the PRKACA gene. We established a PCR-restriction fragment length polymorphism assay and revealed that the mutated allele was expressed at a similar level to the wild-type allele. These findings demonstrated that 1) the prevalence of Japanese patients with CPA who showed overt Cushing's syndrome and whose somatic mutations in the PRKACA gene was similar to that in Western countries, 2) the mutation might be specific for CPAs causing overt Cushing's syndrome, and 3) the mutant PRKACA allele was expressed appropriately in CPAs.
authors: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.
authors: Yasuyo
authors: Y
authors: Nakajima
authors: Takashi
authors: T
authors: Okamura
authors: Tamae
authors: T
authors: Gohko
authors: Tetsurou
authors: T
authors: Satoh
authors: Koshi
authors: K
authors: Hashimoto
authors: Nobuyuki
authors: N
authors: Shibusawa
authors: Atsushi
authors: A
authors: Ozawa
authors: Sumiyasu
authors: S
authors: Ishii
authors: Takuya
authors: T
authors: Tomaru
authors: Kazuhiko
authors: K
authors: Horiguchi
authors: Shuichi
authors: S
authors: Okada
authors: Daisuke
authors: D
authors: Takata
authors: Nana
authors: N
authors: Rokutanda
authors: Jun
authors: J
authors: Horiguchi
authors: Yoshito
authors: Y
authors: Tsushima
authors: Tetsunari
authors: T
authors: Oyama
authors: Izumi
authors: I
authors: Takeyoshi
authors: Masanobu
authors: M
authors: Yamada
mesh_terms: D000236:Adenoma / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism*; D000310:Adrenal Gland Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism*; D000328:Adult; D000368:Aged; D003480:Cushing Syndrome / Q000453:epidemiology / Q000235:genetics; D054751:Cyclic AMP-Dependent Protein Kinase Catalytic Subunits / Q000235:genetics*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D007564:Japan / Q000453:epidemiology; D008875:Middle Aged; D009154:Mutation; D009378:Neoplasms, Multiple Primary / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D012150:Polymorphism, Restriction Fragment Length; D012189:Retrospective Studies
chemical_list: D054751:Cyclic AMP-Dependent Protein Kinase Catalytic Subunits; C517757:PRKACA protein, human; D006854:Hydrocortisone