{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T12:40:30Z","timestamp":1787920830346,"version":"build-2784847793"},"reference-count":37,"publisher":"The Endocrine Society","issue":"10","funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["ZIA DK043006-46"],"award-info":[{"award-number":["ZIA DK043006-46"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute for Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012728","name":"Frederick National Laboratory","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012728","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,9,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Parathyroid cancer (PC) is a rare endocrine neoplasm with high mortality. While surgery is the treatment for patients with the disease, recurrence rates are high, and patients usually succumb to severe hypercalcemia. There is no effective systemic therapy for the disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate for novel genes causing parathyroid cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed the germline DNA of 17 patients with \u201csporadic\u201d PC and 3 with atypical parathyroid tumors (APTs) who did not have germline CDC73 or MEN1 pathogenic variants. Sequencing of available tumor tissue from 14 patients with PC and 2 with APT was also performed (including 2 patients with no available germline DNA). In addition, sporadic parathyroid adenomas from 74 patients were analyzed for FLCN variants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified germline FLCN variants in 3 unrelated patients with PC. The 2 frameshift variants have been described in patients with Birt-Hogg-Dub\u00e9 (BHD) syndrome, while the pathogenicity of the missense variant c.124G &amp;gt; C (p.G42R) has not been definitively established. Functional analysis of the missense variant showed a potential effect on posttranslational modification. All 3 patients with germline FLCN variants were noted to have renal cysts and 2 had lung cysts, features associated with BHD syndrome. Somatic FLCN variants were identified in tumors from 2 (1 APT) of 16 patients with PC\/APT and in none of the 74 sporadic parathyroid adenomas. No second hits in FLCN were noted on sequencing; however, loss of heterozygosity at the locus was demonstrated in 2 of 3 patients with the identified germline FLCN variant.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The finding of FLCN variants associated with PC may provide the foundation for the development of therapy for this malignancy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgad136","type":"journal-article","created":{"date-parts":[[2023,3,20]],"date-time":"2023-03-20T00:36:31Z","timestamp":1679272591000},"page":"2686-2698","source":"Crossref","is-referenced-by-count":17,"title":["Germline- and Somatic-Inactivating\n                    <i>FLCN<\/i>\n                    Variants in Parathyroid Cancer and Atypical Parathyroid Tumors"],"prefix":"10.1210","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9201-3340","authenticated-orcid":false,"given":"Smita","family":"Jha","sequence":"first","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health , Bethesda, MD 20892 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Welch","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health , Bethesda, MD 20892 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rana","family":"Tora","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health , Bethesda, MD 20892 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Lack","sequence":"additional","affiliation":[{"name":"NIAID Collaborative Bioinformatics Resource, National Institute for Allergy and Infectious Diseases , Bethesda, MD 20892 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Warner","sequence":"additional","affiliation":[{"name":"Frederick National Laboratory, National Institutes of Health , Bethesda, MD 21701 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9710-4030","authenticated-orcid":false,"given":"Jaydira","family":"del Rivero","sequence":"additional","affiliation":[{"name":"Developmental Therapeutics Branch National Cancer Institute, National Institutes of Health , Bethesda, MD 20892 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samira M","family":"Sadowski","sequence":"additional","affiliation":[{"name":"Endocrine Surgery Section, Surgical Oncology Program , Bethesda, MD 20892 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naris","family":"Nilubol","sequence":"additional","affiliation":[{"name":"Endocrine Surgery Section, Surgical Oncology Program , Bethesda, MD 20892 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura S","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, MD 20892 , USA"},{"name":"Frederick National Laboratory for Cancer Research, Basic Science Program , Frederick, MD 21701 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W Marston","family":"Linehan","sequence":"additional","affiliation":[{"name":"Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, MD 20892 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee S","family":"Weinstein","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health , Bethesda, MD 20892 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William F","family":"Simonds","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health , Bethesda, MD 20892 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunita K","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health , Bethesda, MD 20892 , 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