{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T05:01:39Z","timestamp":1788930099855,"version":"build-2803163510"},"reference-count":52,"publisher":"The Endocrine Society","issue":"12","license":[{"start":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T00:00:00Z","timestamp":1598918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["314061271"],"award-info":[{"award-number":["314061271"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["FA-466\/8-1"],"award-info":[{"award-number":["FA-466\/8-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["RO-5435\/3-1"],"award-info":[{"award-number":["RO-5435\/3-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005972","name":"Deutsche Krebshilfe","doi-asserted-by":"publisher","award":["70113526"],"award-info":[{"award-number":["70113526"]}],"id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005972","name":"Deutsche Krebshilfe","doi-asserted-by":"publisher","award":["70112617"],"award-info":[{"award-number":["70112617"]}],"id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003042","name":"Else Kr\u00f6ner-Fresenius-Stiftung","doi-asserted-by":"publisher","award":["2015_A228"],"award-info":[{"award-number":["2015_A228"]}],"id":[{"id":"10.13039\/501100003042","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Italian Ministry of Health","award":["RF-GR-2018-12365398"],"award-info":[{"award-number":["RF-GR-2018-12365398"]}]},{"name":"Italian Ministry of Health","award":["RF-2013-02356606"],"award-info":[{"award-number":["RF-2013-02356606"]}]},{"name":"Italian Ministry of University and Research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Pathogenesis of autonomous steroid secretion and adrenocortical tumorigenesis remains partially obscure.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To investigate the relationship between transcriptome profile and genetic background in a large series of adrenocortical tumors and identify new potential pathogenetic mechanisms.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>Cross-sectional study.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Setting<\/jats:title>\n                  <jats:p>University Hospitals of the European Network for the Study of Adrenal Tumors (ENSAT).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Patients<\/jats:title>\n                  <jats:p>We collected snap-frozen tissue from patients with adrenocortical tumors (n = 59) with known genetic background: 26 adenomas with Cushing syndrome (CS- cortisol-producing adenoma [CPA]), 17 adenomas with mild autonomous cortisol secretion (MACS-CPAs), 9 endocrine-inactive adenomas (EIAs), and 7 adrenocortical carcinomas (ACCs).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Intervention<\/jats:title>\n                  <jats:p>Ribonucleic acid (RNA) sequencing.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Main Outcome Measures<\/jats:title>\n                  <jats:p>Gene expression, long noncoding RNA (lncRNA) expression, and gene fusions. Correlation with genetic background defined by targeted Sanger sequencing, targeted panel- or whole-exome sequencing.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Transcriptome analysis identified 2 major clusters for adenomas: Cluster 1 (n = 32) mainly consisting of MACS-CPAs with CTNNB1 or without identified driver mutations (46.9% of cases) and 8\/9 EIAs; Cluster 2 (n = 18) that comprised CP-CPAs with or without identified driver mutation in 83.3% of cases (including all CS-CPAs with PRKACA mutation). Two CS-CPAs, 1 with CTNNB1 and 1 with GNAS mutation, clustered separately and relatively close to ACC. lncRNA analysis well differentiate adenomas from ACCs. Novel gene fusions were found, including AKAP13-PDE8A in one CS-CPA sample with no driver mutation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>MACS-CPAs and EIAs showed a similar transcriptome profile, independently of the genetic background, whereas most CS-CPAs clustered together. Still unrevealed molecular alterations in the cAMP\/PKA or Wnt\/beta catenin pathways might be involved in the pathogenesis of adrenocortical tumors.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgaa616","type":"journal-article","created":{"date-parts":[[2020,9,2]],"date-time":"2020-09-02T02:55:35Z","timestamp":1599015335000},"page":"e4459-e4473","source":"Crossref","is-referenced-by-count":37,"title":["RNA Sequencing and Somatic Mutation Status of Adrenocortical Tumors: Novel Pathogenetic Insights"],"prefix":"10.1210","volume":"105","author":[{"given":"Guido","family":"Di Dalmazi","sequence":"first","affiliation":[{"name":"Endocrinology Unit, Department of Medical and Surgical Sciences, University of Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2616-3249","authenticated-orcid":false,"given":"Barbara","family":"Altieri","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital, University of W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claus","family":"Scholz","sequence":"additional","affiliation":[{"name":"Life and Medical Sciences Institute, University of Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6271-5533","authenticated-orcid":false,"given":"Silviu","family":"Sbiera","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital, University of W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Luconi","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences, University of Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Waldman","sequence":"additional","affiliation":[{"name":"Mivendo Klinik Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darko","family":"Kastelan","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, University Hospital Center Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"Ceccato","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Medicine DIMED, University-Hospital of Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7594-3300","authenticated-orcid":false,"given":"Iacopo","family":"Chiodini","sequence":"additional","affiliation":[{"name":"Istituto Auxologico Italiano, IRCCS, Unit for Bone Metabolism Diseases and Diabetes & Lab of Endocrine and Metabolic Research, Milan, Italy"},{"name":"University of Milan, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Arnaldi","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Riester","sequence":"additional","affiliation":[{"name":"Medizinische Klinik und Poliklinik IV, Klinikum der Universit\u00e4t M\u00fcnchen, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Osswald","sequence":"additional","affiliation":[{"name":"Medizinische Klinik und Poliklinik IV, Klinikum der Universit\u00e4t M\u00fcnchen, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7826-3984","authenticated-orcid":false,"given":"Felix","family":"Beuschlein","sequence":"additional","affiliation":[{"name":"Medizinische Klinik 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Comprehensive Cancer Center Mainfranken, University of W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5020-2071","authenticated-orcid":false,"given":"Cristina L","family":"Ronchi","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital, University of W\u00fcrzburg, W\u00fcrzburg, Germany"},{"name":"Institute of Metabolism and Systems Research, University of Birmingham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2020,9,1]]},"reference":[{"key":"2021122106255142400_CIT0001","first-page":"4252","volume-title":"Cushing Syndrome-Unilateral Adrenal Adenoma. 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