{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:18:36Z","timestamp":1792001916857,"version":"4.4.0"},"reference-count":0,"publisher":"Bioscientifica","issue":"11","license":[{"start":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T00:00:00Z","timestamp":1635724800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,11,1]]},"abstract":"\n Patients with the multiple endocrine neoplasia type 1 (MEN1) syndrome carry germline heterozygous loss-of-function mutations in the\n MEN1<\/jats:italic>\n gene which predisposes them to develop various endocrine and non-endocrine tumors. Over 90% of the tumors show loss of heterozygosity (LOH) at chromosome 11q13, the\n MEN1<\/jats:italic>\n locus, due to somatic loss of the wild-type\n MEN1<\/jats:italic>\n allele. Thymic neuroendocrine tumors (NETs) or thymic carcinoids are uncommon in MEN1 patients but are a major cause of mortality. LOH at the\n MEN1<\/jats:italic>\n locus has not been demonstrated in thymic tumors. The goal of this study was to investigate the molecular aspects of MEN1-associated thymic tumors including LOH at the\n MEN1<\/jats:italic>\n locus and RNA-sequencing (RNA-Seq) to identify genes associated with tumor development and potential targeted therapy. A retrospective chart review of 294 patients with\n MEN1<\/jats:italic>\n germline mutations identified 14 patients (4.8%) with thymic tumors (12 thymic NETs and 2 thymomas). LOH at the\n MEN1<\/jats:italic>\n locus was identified in 10 tumors including the 2 thymomas, demonstrating that somatic LOH at the\n MEN1<\/jats:italic>\n locus is also the mechanism for thymic tumor development. Unsupervised principal component analysis and hierarchical clustering of RNA-Seq data showed that thymic NETs formed a homogenous transcriptomic group separate from thymoma and normal thymus.\n KSR2<\/jats:italic>\n (kinase suppressor of Ras 2), that promotes Ras-mediated signaling, was abundantly expressed in thymic NETs, a potential therapeutic target. The molecular insights gained from our study about thymic tumors combined with similar data from other MEN1-associated tumors may lead to better surveillance and treatment of these rare tumors.\n <\/jats:p>","DOI":"10.1530\/erc-21-0226","type":"journal-article","created":{"date-parts":[[2021,9,13]],"date-time":"2021-09-13T11:50:37Z","timestamp":1631533837000},"page":"L15-L19","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":17,"title":["Two distinct classes of thymic tumors in patients with MEN1 show LOH at the MEN1 locus"],"prefix":"10.1530","volume":"28","author":[{"given":"Adel","family":"Mandl","sequence":"first","affiliation":[{"name":"1Metabolic Diseases Branch, Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James M","family":"Welch","sequence":"additional","affiliation":[{"name":"1Metabolic Diseases Branch, Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gayathri","family":"Kapoor","sequence":"additional","affiliation":[{"name":"1Metabolic Diseases Branch, Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaishali I","family":"Parekh","sequence":"additional","affiliation":[{"name":"1Metabolic Diseases Branch, Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S","family":"Schrump","sequence":"additional","affiliation":[{"name":"2Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R Taylor","family":"Ripley","sequence":"additional","affiliation":[{"name":"3Division of General Thoracic Surgery, Baylor College of Medicine, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary F","family":"Walter","sequence":"additional","affiliation":[{"name":"4NIDDK Clinical Core, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaydira","family":"Del Rivero","sequence":"additional","affiliation":[{"name":"2Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Smita","family":"Jha","sequence":"additional","affiliation":[{"name":"1Metabolic Diseases Branch, Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William F","family":"Simonds","sequence":"additional","affiliation":[{"name":"1Metabolic Diseases Branch, Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert T","family":"Jensen","sequence":"additional","affiliation":[{"name":"5Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee S","family":"Weinstein","sequence":"additional","affiliation":[{"name":"1Metabolic Diseases Branch, Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny E","family":"Blau","sequence":"additional","affiliation":[{"name":"1Metabolic Diseases Branch, Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunita K","family":"Agarwal","sequence":"additional","affiliation":[{"name":"1Metabolic Diseases Branch, Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","container-title":["Endocrine-Related Cancer"],"original-title":[],"link":[{"URL":"https:\/\/erc.bioscientifica.com\/view\/journals\/erc\/28\/11\/ERC-21-0226.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/erc.bioscientifica.com\/downloadpdf\/journals\/erc\/28\/11\/ERC-21-0226.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:56:08Z","timestamp":1784555768000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/erc\/article\/28\/11\/L15-L19\/25458"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,1]]},"references-count":0,"journal-issue":{"issue":"11"},"URL":"https:\/\/doi.org\/10.1530\/erc-21-0226","relation":{},"ISSN":["1351-0088","1479-6821"],"issn-type":[{"value":"1351-0088","type":"print"},{"value":"1479-6821","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,1]]}}}