EYES2019 7th ESE Young Endocrinologists and Scientists (EYES) Meeting Oral Presentations (67 abstracts)
Transcriptome profiling explains clinical characteristics of PRKACA mutant cortisol-producing adenomas
Jung Hee Kim 1, , Insoon Jang 2 , Su-Jin Kim 3 , Ra-Young Song 3 , Kwang Soo Kim 2 , Hyun-Seob Lee 2 , Moon Woo Seong 4 , Chan Soo Shin 1 & Kyu Eun Lee 3
1Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; 2Translational Research Institute, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea; 3Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea; 4Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; 5Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University College of Medicine, Seoul, Republic of Korea.
Objectives: The activating mutation (L206R) in PRKACA has been reported in more than 30–50% of cases with cortisol-producing adenomas (CPAs). We aimed to compare the clinical characteristics and gene expression profiling between PRKACA L206R mutant and wild type CPAs.
Methods: We included 57 subjects with CPAs who underwent adrenalectomy at Seoul National University Hospital. Sanger sequencing for PRKACA was conducted in 57 CPA tumor tissues. RNA sequencing was performed in 13 fresh frozen tumor tissues.
Result: The prevalence of PRKACA L206R mutation was 53% (30/57). The mean age of study subjects was 42±12 years and female was 89.5% (7/57). Subjects with PRKACA L206R mutant CPAs showed smaller adenoma size (3.24±0.72 vs. 3.87±1.30 cm, P=0.044) and lower DHEA-S level (221±176 vs. 1511±3307 ng/ml, P=0.001) than those with PRKACA wild type CPAs. Transcriptome profiling showed that 244 differentially expressed genes between PRKACA L206R mutant (n=8) and wild type CPAs (n=3) were identified including 5 up-regulated and 199 down-regulated in PRKACA L206R mutant CPAs ((|fold change| ≥ 2, P<0.05)). Using the Ingenuity Pathway Analysis, the top upstream regulator of DEGs was CTNNB1. In KEGG pathway, steroid biosynthesis pathway including STAR was up-regulated but Wnt pathway was down-regulated in PRKACA L206R mutant CPAs.
Conclusion: PRKACA alteration in CPAs causes high hormonal activity with a limited proliferative capacity, which was explained by up-regulation of steroidogenesis-related genes and down-regulation of Wnt pathway through PKA activation.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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