{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T17:47:22Z","timestamp":1740160042847,"version":"3.37.3"},"reference-count":31,"publisher":"Korean Endocrine Society","issue":"6","license":[{"start":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T00:00:00Z","timestamp":1638403200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003693","name":"Korea Institute of Science and Technology","doi-asserted-by":"publisher","award":["2E26990-17-098","2E28030-18-033","2E29290-19-019"],"award-info":[{"award-number":["2E26990-17-098","2E28030-18-033","2E29290-19-019"]}],"id":[{"id":"10.13039\/501100003693","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2020R1C1C1010723"],"award-info":[{"award-number":["2020R1C1C1010723"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["e-enm.org"],"crossmark-restriction":true},"short-container-title":["Endocrinol Metab"],"published-print":{"date-parts":[[2021,12,31]]},"abstract":"Background: An activating mutation (c.617A>C\/p.Lys206Arg, L206R) in protein kinase cAMP-activated catalytic subunit alpha (<i>PRKACA<\/i>) has been reported in 35% to 65% of cases of cortisol-producing adenomas (CPAs). We aimed to compare the clinical characteristics and transcriptome analysis between <i>PRKACA<\/i> L206R mutants and wild-type CPAs in Korea.Methods: We included 57 subjects with CPAs who underwent adrenalectomy at Seoul National University Hospital. Sanger sequencing for <i>PRKACA<\/i> was conducted in 57 CPA tumor tissues. RNA sequencing was performed in 13 fresh-frozen tumor tissues.Results: The prevalence of the <i>PRKACA<\/i> L206R mutation was 51% (29\/57). The mean age of the study subjects was 42\u00b112 years, and 87.7% (50\/57) of the patients were female. Subjects with <i>PRKACA<\/i> L206R mutant CPAs showed smaller adenoma size (3.3\u00b10.7 cm vs. 3.8\u00b11.2 cm, <i>P<\/i>=0.059) and lower dehydroepiandrosterone sulfate levels (218\u00b1180 ng\/mL vs. 1,511\u00b13,307 ng\/mL, <i>P<\/i>=0.001) than those with <i>PRKACA<\/i> wild-type CPAs. Transcriptome profiling identified 244 differentially expressed genes (DEGs) between <i>PRKACA<\/i> L206R mutant (<i>n<\/i>=8) and wild-type CPAs (<i>n<\/i>=5), including five upregulated and 239 downregulated genes in <i>PRKACA<\/i> L206R mutant CPAs (|fold change| \u22652, <i>P<\/i><0.05). Among the upstream regulators of DEGs, <i>CTNNB1<\/i> was the most significant transcription regulator. In several pathway analyses, the Wnt signaling pathway was downregulated and the steroid biosynthesis pathway was upregulated in <i>PRKACA<\/i> mutants. Protein-protein interaction analysis also showed that <i>PRKACA<\/i> downregulates Wnt signaling and upregulates steroid biosynthesis.Conclusion: The <i>PRKACA<\/i> L206R mutation in CPAs causes high hormonal activity with a limited proliferative capacity, as supported by transcriptome profiling.<\/jats:p>","DOI":"10.3803\/enm.2021.1217","type":"journal-article","created":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T05:59:45Z","timestamp":1638424785000},"page":"1287-1297","update-policy":"https:\/\/doi.org\/10.3803\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical and Molecular Characteristics of PRKACA L206R Mutant Cortisol-Producing Adenomas in Korean 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