{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T15:36:45Z","timestamp":1791041805827,"version":"4.1.0"},"reference-count":25,"publisher":"Georg Thieme Verlag KG","issue":"08","funder":[{"name":"Health\/National Institute of Diabetes and Digestive and Kidney\n                        Diseases","award":["R01 DK106618"],"award-info":[{"award-number":["R01 DK106618"]}]},{"name":"G.D.H. is supported by the Department of Defense Congressionally\n                        Directed Medical Research Programs","award":["W81XWH-19-1-0623"],"award-info":[{"award-number":["W81XWH-19-1-0623"]}]},{"name":"G.D.H. is supported by the Department of Defense Congressionally\n                        Directed Medical Research Programs","award":["W81XWH-19-1-0528"],"award-info":[{"award-number":["W81XWH-19-1-0528"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Horm Metab Res"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Lack of routine fresh or frozen tissue is a barrier to widespread transcriptomic\n                    analysis of adrenal cortical tumors and an impediment to translational research\n                    in endocrinology and endocrine oncology. Our group has previously pioneered the\n                    use of targeted amplicon-based next-generation sequencing for archival\n                    formalin-fixed paraffin-embedded (FFPE) adrenal tissue specimens to characterize\n                    the spectrum of somatic mutations in various forms of primary aldosteronism.\n                    Herein, we developed and validated a novel 194-amplicon targeted next-generation\n                    RNA sequencing (RNAseq) assay for transcriptomic analysis of adrenal tumors\n                    using clinical-grade FFPE specimens. Targeted RNAseq-derived expression values\n                    for 27 adrenal cortical tumors, including aldosterone-producing adenomas (APA;\n                    n=8), cortisol-producing adenomas (CPA; n=11), and adrenal\n                    cortical carcinomas (ACC; n=8), highlighted known\n                    differentially-expressed genes (DEGs; i.\u2009e., CYP11B2,\n                    IGF2, etc.) and tumor type-specific transcriptional modules\n                    (i.\u2009e., high cell cycle\/proliferation transcript expression in\n                    ACC, etc.), and a subset of DEGs was validated orthogonally using quantitative\n                    reverse transcription PCR (qRT-PCR). Finally, unsupervised hierarchical\n                    clustering using a subset of high-confidence DEGs revealed three discrete\n                    clusters representing APA, CPA, and ACC tumors with corresponding unique gene\n                    expression signatures, suggesting potential clinical utility for a\n                    transcriptomic-based approach to tumor classification. Overall, these data\n                    support the use of targeted amplicon-based RNAseq for comprehensive\n                    transcriptomic profiling of archival FFPE adrenal tumor material and indicate\n                    that this approach may facilitate important translational research opportunities\n                    for the study of these tumors.<\/jats:p>","DOI":"10.1055\/a-1212-8803","type":"journal-article","created":{"date-parts":[[2020,8,13]],"date-time":"2020-08-13T22:34:20Z","timestamp":1597358060000},"page":"607-613","source":"Crossref","is-referenced-by-count":15,"title":["Targeted RNAseq of Formalin-Fixed Paraffin-Embedded Tissue to\n                    Differentiate Among Benign and Malignant Adrenal Cortical Tumors"],"prefix":"10.1055","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5128-6262","authenticated-orcid":false,"given":"Samuel W.","family":"Plaska","sequence":"additional","affiliation":[{"name":"Department of Molecular and Integrative Physiology, University of\n                    Michigan Medical School, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Jen","family":"Liu","sequence":"additional","affiliation":[{"name":"Michigan Center for Translational Pathology, Ann Arbor, Michigan,\n                    USA"},{"name":"Department of Pathology, University of Michigan Medical School, Ann\n                    Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung Soo","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Molecular and Integrative Physiology, University of\n                    Michigan Medical School, Ann Arbor, Michigan, USA"},{"name":"Division of Endocrinology and Metabolism, Department of Internal\n                    Medicine, Yonsei University Wonju College of Medicine, Wonju, South\n                    Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juilee","family":"Rege","sequence":"additional","affiliation":[{"name":"Department of Molecular and Integrative Physiology, University of\n                    Michigan Medical School, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nolan R.","family":"Bick","sequence":"additional","affiliation":[{"name":"Department of Molecular and Integrative Physiology, University of\n                    Michigan Medical School, Ann Arbor, Michigan, USA"},{"name":"Department of Pathology, University of Michigan Medical School, Ann\n                    Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio M.","family":"Lerario","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Metabolism, Endocrinology,\n                    and Diabetes, University of Michigan Medical School, Ann Arbor, Michigan,\n                    USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary D.","family":"Hammer","sequence":"additional","affiliation":[{"name":"Department of Molecular and Integrative Physiology, University of\n                    Michigan Medical School, Ann Arbor, Michigan, USA"},{"name":"Department of Internal Medicine, Division of Metabolism, Endocrinology,\n                    and Diabetes, University of Michigan Medical School, Ann Arbor, Michigan,\n                    USA"},{"name":"Department of Cell & Developmental Biology, University of\n                    Michigan Medical School, Ann Arbor, Michigan, USA"},{"name":"Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan,\n                    USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Giordano","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Michigan Medical School, Ann\n                    Arbor, Michigan, USA"},{"name":"Department of Internal Medicine, Division of Metabolism, Endocrinology,\n                    and Diabetes, University of Michigan Medical School, Ann Arbor, Michigan,\n                    USA"},{"name":"Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan,\n                    USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Else","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Metabolism, Endocrinology,\n                    and Diabetes, University of Michigan Medical School, Ann Arbor, Michigan,\n                    USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott A.","family":"Tomlins","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Michigan Medical School, Ann\n                    Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William E.","family":"Rainey","sequence":"additional","affiliation":[{"name":"Department of Molecular and Integrative Physiology, University of\n                    Michigan Medical School, Ann Arbor, Michigan, USA"},{"name":"Department of Internal Medicine, Division of Metabolism, Endocrinology,\n                    and Diabetes, University of Michigan Medical School, Ann Arbor, Michigan,\n                    USA"},{"name":"Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan,\n                    USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron M.","family":"Udager","sequence":"additional","affiliation":[{"name":"Michigan Center for Translational Pathology, Ann Arbor, Michigan,\n                    USA"},{"name":"Department of Pathology, University of Michigan Medical School, Ann\n                    Arbor, Michigan, USA"},{"name":"Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan,\n                    USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2020,8,13]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.mce.2016.09.003","article-title":"Regulation of zonation and homeostasis in the adrenal cortex","volume":"441","author":"E Pignatti","year":"2017","journal-title":"Mol Cell Endocrinol"},{"key":"ref2","first-page":"3","article-title":"Presidential address. I. Painting background. II","volume":"45","author":"J W Conn","year":"1955","journal-title":"Primary aldosteronism, a new clinical syndrome. J Lab Clin\n                    Med"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1001\/jama.1932.02740560007003","article-title":"Further Notes on Pituitary Basophilism","volume":"99","author":"H Cushing","year":"1932","journal-title":"JAMA"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"R437","DOI":"10.1530\/ERC-16-0055","article-title":"Genetics of primary hyperaldosteronism","volume":"23","author":"R K Dutta","year":"2016","journal-title":"Endocr Relat Cancer"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1126\/science.1252328","article-title":"Recurrent somatic mutations underlie corticotropin-independent Cushing\u2019s\n                    syndrome","volume":"344","author":"Y Sato","year":"2014","journal-title":"Science"},{"key":"ref6","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","author":"S Zheng","year":"2016","journal-title":"Cancer Cell"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1530\/eje.1.02116","article-title":"Analysis by cDNA microarrays of gene expression patterns of human adrenocortical\n                    tumors","volume":"154","author":"E P Slater","year":"2006","journal-title":"Eur J Endocrinol"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1677\/ERC-08-0237","article-title":"Microarray gene expression and immunohistochemistry analyses of adrenocortical\n                    tumors identify IGF2 and Ki-67 as useful in differentiating carcinomas from\n                    adenomas","volume":"16","author":"PS H Soon","year":"2009","journal-title":"Endocr Relat Cancer"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1210\/jc.2015-3239","article-title":"Molecular heterogeneity in aldosterone-producing adenomas","volume":"101","author":"K Nanba","year":"2016","journal-title":"J Clin Endocrinol Metab"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"E4591","DOI":"10.1073\/pnas.1505529112","article-title":"Aldosterone stimulating somatic gene mutations are common in normal adrenal\n                    glands","volume":"112","author":"K Nishimoto","year":"2015","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/j.eururo.2018.06.047","article-title":"Targeted DNA and RNA sequencing of paired urothelial and squamous bladder\n                    cancers reveals discordant genomic and transcriptomic events and unique\n                    therapeutic implications","volume":"74","author":"D H Hovelson","year":"2018","journal-title":"Eur Urol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"e123468","DOI":"10.1172\/jci.insight.123468","article-title":"Transcriptomic heterogeneity in multifocal prostate cancer","volume":"3","author":"S S Salami","year":"2018","journal-title":"JCI Insight"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"W645","DOI":"10.1093\/nar\/gkl229","article-title":"Applications for protein sequence-function evolution data: mRNA\/protein\n                    expression analysis and coding SNP scoring tools","volume":"34","author":"P D Thomas","year":"2006","journal-title":"Nucleic Acids Res"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1161\/HYPERTENSIONAHA.119.14349","article-title":"Somatic CACNA1H mutation as a cause of aldosterone producing adenoma","volume":"75","author":"K Nanba","year":"2020","journal-title":"Hypertension"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1210\/jc.2016-4007","article-title":"Genetic and histopathologic intertumor heterogeneity in primary\n                    aldosteronism","volume":"102","author":"K Omata","year":"2017","journal-title":"J Clin Endocrinol Metab"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1210\/js.2017-00134","article-title":"Aldosterone-producing cell clusters frequently harbor somatic mutations and\n                    accumulate with age in normal adrenals","volume":"1","author":"K Omata","year":"2017","journal-title":"J Endocr Soc"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1161\/HYPERTENSIONAHA.118.11086","article-title":"Cellular and genetic causes of idiopathic hyperaldosteronism","volume":"72","author":"K Omata","year":"2018","journal-title":"Hypertension"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"K37","DOI":"10.1530\/EJE-19-0377","article-title":"A somatic mutation in CLCN2 identified in a sporadic aldosterone-producing\n                    adenoma","volume":"181","author":"R K Dutta","year":"2019","journal-title":"Eur J Endocrinol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"6269","DOI":"10.1038\/s41598-019-41525-2","article-title":"RNA sequencing provides novel insights into the transcriptome of aldosterone\n                    producing adenomas","volume":"9","author":"S Backman","year":"2019","journal-title":"Sci Rep"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1158\/1541-7786.MCR-18-1178","article-title":"Multiclonality and marked branched evolution of low grade endometrioid\n                    endometrial carcinoma","volume":"17","author":"L Lazo de la Vega","year":"2019","journal-title":"Mol Cancer Res"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1158\/1078-0432.CCR-08-1067","article-title":"Molecular classification and prognostication of adrenocortical tumors by\n                    transcriptome profiling","volume":"15","author":"T J Giordano","year":"2009","journal-title":"Clin Cancer Res"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"9327","DOI":"10.1093\/nar\/gkv908","article-title":"Integrated genome-wide analysis of genomic changes and gene regulation in human\n                    adrenocortical tissue samples","volume":"43","author":"S K Gara","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.mce.2011.09.044","article-title":"Gene expression profiling in adrenocortical neoplasia","volume":"351","author":"G Assie","year":"2012","journal-title":"Mol Cell Endocrinol"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/s12022-006-0007-z","article-title":"Molecular pathology of adrenal cortical tumors: separating adenomas from\n                    carcinomas","volume":"17","author":"T J Giordano","year":"2006","journal-title":"Endocr Pathol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1097\/PAS.0000000000000943","article-title":"Diagnostic and prognostic biomarkers of adrenal cortical carcinoma","volume":"42","author":"O Mete","year":"2018","journal-title":"Am J Surg Pathol"}],"container-title":["Hormone and Metabolic Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-1212-8803.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,23]],"date-time":"2022-08-23T23:46:10Z","timestamp":1661298370000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-1212-8803"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8]]},"references-count":25,"journal-issue":{"issue":"08","published-online":{"date-parts":[[2020,8,13]]},"published-print":{"date-parts":[[2020,8]]}},"URL":"https:\/\/doi.org\/10.1055\/a-1212-8803","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0018-5043","1439-4286"],"issn-type":[{"value":"0018-5043","type":"print"},{"value":"1439-4286","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8]]}}}