Clinical characteristics of PRKACA mutations in Chinese patients with adrenal lesions: a single-centre study.
BACKGROUND
Recent studies have identified that the somatic PRKACA L206R mutation can cause cortisol-producing adenomas (CPAs). This study investigated the prevalence and characteristics of PRKACA, GNAS and CTNNB1 mutations in adrenal lesions in patients from a single centre in China.


METHODS
We sequenced PRKACA, GNAS and CTNNB1 genes in 108 patients, including 60 patients with CPAs (57 with unilateral and three with bilateral adenomas), 13 with nonfunctional adenomas, 12 with adrenocortical carcinomas (ACCs), 15 with primary bilateral macronodular hyperplasia (PBMAH) and eight with aldosterone and cortisol cosecreting adenomas. Mutations in PRKACA, GNAS and CTNNB1 were examined, and clinical characteristics were compared.


RESULTS
Among the unilateral CPAs, we identified somatic mutations in PRKACA (L206R) in 23 cases (40·4%), GNAS (R201C and R201H) in six cases (10·5%), CTNNB1 (S45C, L46P and S45P) in six cases (10·5%) and CTNNB1 plus GNAS in two cases (3·5%). PRKACA and GNAS mutations were mutually exclusive. Among the patients with nonfunctional adenoma, two carried CTNNB1 mutations. Among the patients with ACC, two carried GNAS and CTNNB1 mutations but none carried PRKACA mutations. One patient showed bilateral CPA, and one PBMAH patient carried PRKACA mutations. No mutations in PRKACA, GNAS or CTNNB1 were identified in the eight patients with aldosterone and cortisol cosecreting adenomas. PRKACA-mutant adenomas were associated with young age, overt Cushing's syndrome and high cortisol levels compared with non-PRKACA-mutant or CTNNB1-mutant lesions.


CONCLUSIONS
PRKACA mutations are present in CPAs and bilateral adrenal macronodular hyperplasia. PRKACA mutation is associated with more severe autonomous cortisol secretion.
State Key Laboratory of Kidney Disease, Department of Urology, Chinese PLA Medical Academy, Chinese People's Liberation Army General Hospital, Beijing, China.
Xintao
X
Li
State Key Laboratory of Kidney Disease, Department of Urology, Chinese PLA Medical Academy, Chinese People's Liberation Army General Hospital, Beijing, China.
Baojun
B
Wang
State Key Laboratory of Kidney Disease, Department of Urology, Chinese PLA Medical Academy, Chinese People's Liberation Army General Hospital, Beijing, China.
Lu
L
Tang
Macao Polytechnic Institute School of Health Sciences, Macao, China.
Bin
B
Lang
State Key Laboratory of Kidney Disease, Department of Urology, Chinese PLA Medical Academy, Chinese People's Liberation Army General Hospital, Beijing, China.
Yu
Y
Zhang
State Key Laboratory of Kidney Disease, Department of Urology, Chinese PLA Medical Academy, Chinese People's Liberation Army General Hospital, Beijing, China.
Fan
F
Zhang
State Key Laboratory of Kidney Disease, Department of Urology, Chinese PLA Medical Academy, Chinese People's Liberation Army General Hospital, Beijing, China.
Luyao
L
Chen
Department of Outpatient Officer Consultation Room, Chinese PLA Medical Academy, Chinese People's Liberation Army General Hospital, Beijing, China.
Jinzhi
J
Ouyang
State Key Laboratory of Kidney Disease, Department of Urology, Chinese PLA Medical Academy, Chinese People's Liberation Army General Hospital, Beijing, China.
Xu
X
Zhang
D000236:Adenoma; D000310:Adrenal Gland Neoplasms / Q000473:pathology*; D000311:Adrenal Glands / Q000473:pathology; D000328:Adult; D000368:Aged; D002681:China; D002864:Chromogranins / Q000235:genetics; D054751:Cyclic AMP-Dependent Protein Kinase Catalytic Subunits / Q000235:genetics*; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D006965:Hyperplasia; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017422:Sequence Analysis, DNA; D055815:Young Adult; D051176:beta Catenin / Q000235:genetics
C495270:CTNNB1 protein, human; D002864:Chromogranins; D051176:beta Catenin; D054751:Cyclic AMP-Dependent Protein Kinase Catalytic Subunits; C517757:PRKACA protein, human; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs; D006854:Hydrocortisone