{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T15:36:38Z","timestamp":1791041798852,"version":"4.1.0"},"reference-count":47,"publisher":"Bioscientifica","issue":"5","content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:p>\n                    Aldosterone-producing adenomas (APAs) are found in 1.5\u20133.0% of hypertensive patients in primary care and can be cured by surgery. Elucidation of genetic events may improve our understanding of these tumors and ultimately improve patient care. Approximately 40% of APAs harbor a missense mutation in the\n                    <jats:italic>KCNJ5<\/jats:italic>\n                    gene. More recently, somatic mutations in\n                    <jats:italic>CACNA1D<\/jats:italic>\n                    ,\n                    <jats:italic>ATP1A1<\/jats:italic>\n                    and\n                    <jats:italic>ATP2B3<\/jats:italic>\n                    , also important for membrane potential\/intracellular Ca\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    regulation, were observed in APAs. In this study, we analyzed 165 APAs for mutations in selected regions of these genes. We then correlated mutational findings with clinical and molecular phenotype using transcriptome analysis, immunohistochemistry and semiquantitative PCR. Somatic mutations in\n                    <jats:italic>CACNA1D<\/jats:italic>\n                    in 3.0% (one novel mutation),\n                    <jats:italic>ATP1A1<\/jats:italic>\n                    in 6.1% (six novel mutations) and\n                    <jats:italic>ATP2B3<\/jats:italic>\n                    in 3.0% (two novel mutations) were detected. All observed mutations were located in previously described hotspot regions. Patients with tumors harboring mutations in\n                    <jats:italic>CACNA1D<\/jats:italic>\n                    ,\n                    <jats:italic>ATP1A1<\/jats:italic>\n                    and\n                    <jats:italic>ATP2B3<\/jats:italic>\n                    were operated at an older age, were more often male and had tumors that were smaller than those in patients with\n                    <jats:italic>KCNJ5<\/jats:italic>\n                    mutated tumors. Microarray transcriptome analysis segregated\n                    <jats:italic>KCNJ5<\/jats:italic>\n                    mutated tumors from\n                    <jats:italic>ATP1A1<\/jats:italic>\n                    \/\n                    <jats:italic>ATP2B3<\/jats:italic>\n                    mutated tumors and those without mutation. We observed significant transcription upregulation of CYP11B2, as well as the previously described glomerulosa-specific gene\n                    <jats:italic>NPNT<\/jats:italic>\n                    , in\n                    <jats:italic>ATP1A1<\/jats:italic>\n                    \/\n                    <jats:italic>ATP2B3<\/jats:italic>\n                    mutated tumors compared to\n                    <jats:italic>KCNJ5<\/jats:italic>\n                    mutated tumors. In summary, we describe novel somatic mutations in proteins regulating the membrane potential\/intracellular Ca\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    levels, and also a distinct mRNA and clinical signature, dependent on genetic alteration.\n                  <\/jats:p>","DOI":"10.1530\/erc-15-0321","type":"journal-article","created":{"date-parts":[[2015,8,18]],"date-time":"2015-08-18T23:19:40Z","timestamp":1439939980000},"page":"735-744","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":80,"title":["Novel somatic mutations and distinct molecular signature in aldosterone-producing adenomas"],"prefix":"10.1530","volume":"22","author":[{"given":"Tobias","family":"\u00c5kerstr\u00f6m","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger Sven","family":"Willenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenko","family":"Cupisti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Ip","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Backman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Moser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajani","family":"Maharjan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce","family":"Robinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K Alexander","family":"Iwen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henning","family":"Dralle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"D Volpe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"B\u00e4ckdahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Botling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"St\u00e5lberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunnar","family":"Westin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin K","family":"Walz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendrik","family":"Lehnert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stan","family":"Sidhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Zedenius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peyman","family":"Bj\u00f6rklund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Hellman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"2015081820185466000_22.5.735.1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0041926"},{"key":"2015081820185466000_22.5.735.2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.111.186239"},{"key":"2015081820185466000_22.5.735.3","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-2965"},{"key":"2015081820185466000_22.5.735.4","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2716"},{"key":"2015081820185466000_22.5.735.5","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2550"},{"key":"2015081820185466000_22.5.735.6","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.110.158543"},{"key":"2015081820185466000_22.5.735.7","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.111.186478"},{"key":"2015081820185466000_22.5.735.8","unstructured":"Brilla CG Weber K 1992 Mineralocorticoid excess, dietary sodium, and myocardial fibrosis. 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