{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:13:37Z","timestamp":1787022817877,"version":"build-2736575974"},"reference-count":43,"publisher":"Bioscientifica","issue":"9","content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,9,1]]},"abstract":"<jats:p>\n                    Adrenal incidentalomas are the most frequent human neoplasms. Recent genomic investigations on functional adrenocortical tumors have demonstrated that somatic mutations in\n                    <jats:italic>PRKACA<\/jats:italic>\n                    and\n                    <jats:italic>KCNJ5<\/jats:italic>\n                    responsible for the development of adrenocortical adenomas (ACAs) are associated with hypercortisolism and aldosteronism, respectively. Several studies have identified\n                    <jats:italic>CTNNB1<\/jats:italic>\n                    mutations in ACAs and have been mostly involved in the tumorigenesis of non-functional ACA (NFACA). However, integrated genomic characterization of NFACAs is lacking. In the current study, we utilized pan-genomic methods to comprehensively analyze 60 NFACA samples. A total of 1264 somatic mutations in coding regions among the 60 samples were identified, with a median of 15 non-silent mutations per tumor. Twenty-two NFACAs (36.67%) had genetic alterations in\n                    <jats:italic>CTNNB1<\/jats:italic>\n                    . We also identified several somatic mutations in genes of the cAMP\/PKA pathway and\n                    <jats:italic>KCNJ5<\/jats:italic>\n                    . Histone modification genes (\n                    <jats:italic>KMT2A<\/jats:italic>\n                    ,\n                    <jats:italic>KMT2C,<\/jats:italic>\n                    and\n                    <jats:italic>KMT2D<\/jats:italic>\n                    ) were altered in 10% of cases. Germline mutations of\n                    <jats:italic>MEN1<\/jats:italic>\n                    and\n                    <jats:italic>RET<\/jats:italic>\n                    were also found. Finally, by comparison of our transcriptome data with those available in the TCGA, we illustrated the molecular characterization of NFACA. We revealed the genetic profiling and molecular landscape of NFACA. Wnt\/\u03b2-catenin pathway activation as shown ssby nuclear and\/or cytoplasmic \u03b2-catenin accumulation is frequent, occurring in about one\u2013third of ACA cases. cytochrome P450 enzymes could be markers to reveal the functional status of adrenocortical tumors. These observations strongly suggest the involvement of the Wnt\/\u03b2-catenin pathway in benign adrenal tumorigenesis and possibly in the regulation of steroid secretion.\n                  <\/jats:p>","DOI":"10.1530\/erc-21-0410","type":"journal-article","created":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T09:32:24Z","timestamp":1655890344000},"page":"521-532","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":6,"title":["Mutational landscape of non-functional adrenocortical adenomas"],"prefix":"10.1530","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5000-0397","authenticated-orcid":true,"given":"Luming","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3278-2812","authenticated-orcid":true,"given":"Jing","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4316-8922","authenticated-orcid":true,"given":"Yan","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6472-3492","authenticated-orcid":true,"given":"Tingwei","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0423-1282","authenticated-orcid":true,"given":"Lei","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2003-7743","authenticated-orcid":true,"given":"Weiwei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2078-8125","authenticated-orcid":true,"given":"Yiran","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1847-9991","authenticated-orcid":true,"given":"Cui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2175-3437","authenticated-orcid":true,"given":"Xu","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3848-7040","authenticated-orcid":true,"given":"Yanan","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People\u2019s Republic of 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