S-Space College of Medicine/School of Medicine (의과대학/대학원) Dept. of Medicine (의학과) Theses (Master's Degree_의학과)
Protein kinase, cAMP-dependent, alpha catalytic subunit (PRKACA) mutation in adrenal Cushing’s syndrome in Korean patients
한국인 부신성 쿠싱 증후군에서의 cAMP-의존 단백질인산화효소 알파 촉매소단위체 (PRKACA) 돌연변이
- Ra-Yeong Song
- 의과대학 의학과
- Issue Date
- 서울대학교 대학원
- 학위논문 (석사)-- 서울대학교 대학원 : 의학과 외과학 전공, 2016. 2. 이규언.
- Introduction: Alterations in the cyclic AMP-protein kinase A signaling pathway have been suggested as a cause of autonomous overproduction of cortisol in adrenocortical tumors, resulting in adrenal Cushing’s syndrome. Somatic and germline mutations in PRKACA, the gene encoding the catalytic subunit alpha of PKA, have been recently identified in 35~65.5% of ACAs associated with overt Cushing’s syndrome. The aim of our study was to validate the hotspot mutation Leu206Arg (c.617AC) in Korean patients, and to analyze the clinical features.
Methods: A retrospective review was conducted on 68 patients who underwent adrenalectomy for overt Cushing’s syndrome (CS) from January 2000 to December 2013 at Seoul National University Hospital. We performed PRKACA sequencing of DNA from formalin fixed paraffin-embedded (FFPE) blocks of 55 patients of whom specimens were available.
Results: PRKACA sequencing for the hotspot mutation Leu206Arg was successful in 48 (87.3%) of 55 DNA samples from FFPE blocks that were available. Leu206Arg PRKACA mutation was found in 20 patients (45.5% of adenoma patients). Patients with PRKACA mutation had significantly lower levels of DHEA-S compared to patients without PRKACA mutation (median 193.0 ng/ml vs. 473.0 ng/ml, p=0.001). Patients with mutated adenomas tended to be older in age (43.9 ± 12.2 vs. 39.5 ± 12.1 years), and were also likely to have more comorbidities such as hypertension and type 2 diabetes. The mean size of adenoma was slightly smaller in patients with PRKACA mutation (3.2 ± 0.9 vs. 3.8 ± 1.1cm).
Conclusions: PRKACA mutation could be complexly associated with the entire adrenal steroidogenesis pathway. Adrenal Cushing’s syndrome patients with this mutation have lower levels of serum DHEA-S
show specific clinical features such as central obesity, buffalo hump, and dry skin
and also seem to have some kind of protection against amenorrhea. In this sample of patients, PRKACA mutation was not associated with any difference in biochemical features compared to those without mutation. Further analysis of a larger number of patients is warranted.