{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T14:39:54Z","timestamp":1790260794693,"version":"4.1.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,5,14]],"date-time":"2021-05-14T00:00:00Z","timestamp":1620950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>Hyperparathyroidism is the third most common endocrine disease. Parathyroid adenoma (PA) accounts for approximately 85% of cases of primary hyperparathyroidism, but the molecular mechanism is not fully understood. Herein, we aimed to investigate the genetic and transcriptomic profiles of sporadic PA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Whole-exome sequencing (WES) and transcriptome sequencing (RNA-seq) of 41 patients with PA and RNA-seq of 5 normal parathyroid tissues were performed. Gene mutations and characterized expression changes were identified. To elucidate the molecular mechanism underlying PA, unsupervised consensus clustering of RNA-seq data was performed. The correlations between the sequencing data and clinicopathological features of these patients were analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Previously reported PA driver gene mutations, such as <jats:italic>MEN1<\/jats:italic> (9\/41), <jats:italic>mTOR<\/jats:italic> (4\/41), <jats:italic>ZFX<\/jats:italic> (3\/41), <jats:italic>CASR<\/jats:italic> (3\/41), <jats:italic>EZH2<\/jats:italic> (2\/41) and <jats:italic>FAT1<\/jats:italic> (2\/41), were also identified in our cohort. Furthermore, somatic mutation of <jats:italic>EZH1<\/jats:italic>, which had not been reported in PA, was found in 4 samples. RNA-seq showed that the expression levels of 84 genes were upregulated and 646 were downregulated in PA samples compared with normal samples. Unsupervised clustering analysis of RNA-seq data clustered these patients into 10 subgroups related to mutation or abnormal expression of a group of potential pathogenic genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:italic>MEN1<\/jats:italic>, <jats:italic>EZH2<\/jats:italic>, <jats:italic>CASR<\/jats:italic>, <jats:italic>EZH1, ZFX<\/jats:italic>, <jats:italic>mTOR<\/jats:italic> and <jats:italic>FAT1<\/jats:italic> mutations in PA were\u00a0revealed. According to the RNA-seq data clustering analysis, cyclin D1, \u03b2-catenin, VDR, CASR and GCM2 may be important factors contributing to the PA gene expression\u00a0profile.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2021.631680","type":"journal-article","created":{"date-parts":[[2021,5,14]],"date-time":"2021-05-14T07:41:05Z","timestamp":1620978065000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":28,"title":["Integrated Whole-Exome and Transcriptome Sequencing of Sporadic Parathyroid Adenoma"],"prefix":"10.3389","volume":"12","author":[{"given":"Ya","family":"Hu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ou","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Surong","family":"Hua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,5,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-4022","article-title":"Incidence and Prevalence of Primary Hyperparathyroidism in a Racially Mixed Population","volume":"98","author":"Yeh","year":"2013","journal-title":"J Clin Endocrinol Metab"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/s0039-6060(97)90357-3","article-title":"Population-Based Screening for Primary Hyperparathyroidism with Serum Calcium and Parathyroid Hormone Values in Menopausal Women","volume":"121","author":"Lundgren","year":"1997","journal-title":"Surgery"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-2303","article-title":"Whole-Exome Sequencing Studies of Nonhereditary (Sporadic) Parathyroid Adenomas","volume":"97","author":"Newey","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1210\/en.2018-00246","article-title":"Whole-Exome Sequencing Identifies Novel Recurrent Somatic Mutations in Sporadic Parathyroid Adenomas","volume":"159","author":"Wei","year":"2018","journal-title":"Endocrinology"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3390\/jcm8030297","article-title":"Comparative Gene Expression Profiles in Parathyroid Adenoma and Normal Parathyroid Tissue","volume":"8","author":"Chai","year":"2019","journal-title":"J Clin Med"},{"key":"B6","article-title":"WHO\/IARC Classification of Tumours","volume-title":"WHO Classification of Tumours of Endocrine Organs. 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