{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T04:00:03Z","timestamp":1790049603802,"version":"4.0.1"},"reference-count":22,"publisher":"Bioscientifica","issue":"2","content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:p>Several somatic mutations specific to aldosterone-producing adenomas (APAs) have been described. A small proportion of adrenocortical carcinomas (ACCs) are associated with hyperaldosteronism, either primary aldosteronism or hyperreninemic hyperaldosteronism. However, it is unknown whether they harbor mutations of the same spectrum as APAs. The objective of this study is to describe the clinical phenotype and molecular genotype of ACCs with hyperaldosteronism, particularly the analysis for common APA-associated genetic changes. Patients were identified by retrospective chart review at a specialized referral center and by positive staining for CYP11B2 of tissue microarrays. Twenty-five patients with ACC and hyperaldosteronism were initially identified by retrospective chart review, and tissue for further analysis was available on 13 tumors. Seven patients were identified by positive staining for CYP11B2 in a tissue microarray, of which two were already identified in the initial chart review. Therefore, a total number of 18 patients with a diagnosis of ACC and features of either primary aldosteronism or hyperreninemic hyperaldosteronism were therefore included in the final study. Mutational status for a select list of oncogenes, tumor suppressor genes and genes known to carry mutations in APAs were analyzed by next-generation sequencing. Review of clinical data suggested autonomous aldosterone production in the majority of cases, while for some cases, hyperreninemic hyperaldosteronism was the more likely mechanism. The mutational landscape of ACCs associated with hyperaldosteronism was not different from ACCs with a different hormonal phenotype. None of the ACCs harbored mutations of known APA-associated genes, suggesting an alternative mechanism conferring aldosterone production.<\/jats:p>","DOI":"10.1530\/erc-18-0385","type":"journal-article","created":{"date-parts":[[2018,11,19]],"date-time":"2018-11-19T12:26:53Z","timestamp":1542630413000},"page":"217-225","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":13,"title":["Somatic mutations in adrenocortical carcinoma with primary aldosteronism or hyperreninemic hyperaldosteronism"],"prefix":"10.1530","volume":"26","author":[{"given":"Isobel C","family":"Mouat","sequence":"first","affiliation":[{"name":"1Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kei","family":"Omata","sequence":"additional","affiliation":[{"name":"1Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA"},{"name":"2Michigan Center for Translational Pathology, Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew S","family":"McDaniel","sequence":"additional","affiliation":[{"name":"1Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA"},{"name":"2Michigan Center for Translational Pathology, Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Namita G","family":"Hattangady","sequence":"additional","affiliation":[{"name":"3Division of Metabolism, Endocrinology & Diabetes, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debnita","family":"Talapatra","sequence":"additional","affiliation":[{"name":"3Division of Metabolism, Endocrinology & Diabetes, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andi K","family":"Cani","sequence":"additional","affiliation":[{"name":"1Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA"},{"name":"2Michigan Center for Translational Pathology, Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel H","family":"Hovelson","sequence":"additional","affiliation":[{"name":"2Michigan Center for Translational Pathology, Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA"},{"name":"4Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott A","family":"Tomlins","sequence":"additional","affiliation":[{"name":"1Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA"},{"name":"2Michigan Center for Translational Pathology, Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA"},{"name":"5Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan, USA"},{"name":"6Department of Urology, University of Michigan Medical School, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William E","family":"Rainey","sequence":"additional","affiliation":[{"name":"7Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary D","family":"Hammer","sequence":"additional","affiliation":[{"name":"3Division of Metabolism, Endocrinology & Diabetes, Department of Internal Medicine, 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hypertension with primary aldosteronism","volume":"4","year":"2015","journal-title":"ELife"},{"key":"ref211","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.ccell.2016.07.013","article-title":"Comprehensive pan-genomic characterization of adrenocortical carcinoma","volume":"30","year":"2016","journal-title":"Cancer Cell"},{"key":"ref101","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1002\/pbc.20938","article-title":"Renin-induced hypertension in Wilms tumor patients","volume":"48","year":"2007","journal-title":"Pediatric Blood and Cancer"},{"key":"ref201","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1007\/s00428-014-1699-y","article-title":"Tumor evolution and progression in multifocal and paired non-invasive\/invasive urothelial carcinoma","volume":"466","year":"2015","journal-title":"Virchows Archiv"},{"key":"ref21","first-page":"440-4","article-title":"Somatic mutations in ATP1A1 and ATP2B3 lead to aldosterone-producing adenomas and secondary hypertension","volume":"45","year":"2013","journal-title":"Nature Genetics"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1126\/science.1198785","article-title":"K+ channel mutations in adrenal aldosterone-producing adenomas and hereditary hypertension.","volume":"331","year":"2011","journal-title":"Science"},{"key":"ref121","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.mce.2014.09.015","article-title":"Understanding primary aldosteronism: impact of next generation sequencing and expression profiling","volume":"399","year":"2015","journal-title":"Molecular and Cellular Endocrinology"},{"key":"ref81","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1161\/01.HYP.8.10.951","article-title":"A case of adrenal tumor producing renin, aldosterone, and sex steroid 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landscape of somatic mutations and copy number alterations in adrenocortical carcinoma of and https org","journal-title":"Journal Clinical Endocrinology Metabolism"},{"key":"ref171","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1038\/ng.2695","article-title":"Somatic and germline CACNA1D calcium channel mutations in aldosterone-producing adenomas and primary aldosteronism","volume":"45","year":"2013","journal-title":"Nature Genetics"}],"container-title":["Endocrine-Related 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