{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:20:21Z","timestamp":1784557221058,"version":"3.55.0"},"reference-count":0,"publisher":"Bioscientifica","issue":"9","content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,9]]},"abstract":"\n Mutation of the\n CDC73<\/jats:italic>\n gene, which encodes parafibromin, has been linked with parathyroid cancer. However, no correlation between genotypes of germline\n CDC73<\/jats:italic>\n mutations and the risk of parathyroid cancer has been known. In this study, subjects with germline\n CDC73<\/jats:italic>\n mutations were identified from the participants of two clinical protocols at National Institutes of Health (Discovery Cohort) and from the literature (Validation Cohort). The relative risk of developing parathyroid cancer was analyzed as a function of\n CDC73<\/jats:italic>\n genotype, and the impact of representative mutations on structure of parafibromin was compared between genotype groups. A total of 419 subjects, 68 in Discovery Cohort and 351 in Validation Cohort, were included. In both cohorts, percentages of\n CDC73<\/jats:italic>\n germline mutations that predicted significant conformational disruption or loss of expression of parafibromin (referred as \u2018high-impact mutations\u2019) were significantly higher among the subjects with parathyroid cancers compared to all other subjects. The Kaplan\u2013Meier analysis showed that high-impact mutations were associated with a 6.6-fold higher risk of parathyroid carcinoma compared to low-impact mutations, despite a similar risk of developing primary hyperparathyroidism between two groups. Disruption of the C-terminal domain (CTD) of parafibromin is directly involved in predisposition to parathyroid carcinoma, since only the mutations impacting this domain were associated with an increased risk of parathyroid carcinoma. Structural analysis revealed that a conserved surface structure in the CTD is universally disrupted by the mutations affecting this domain. In conclusion, high-impact germline\n CDC73<\/jats:italic>\n mutations were found to increase risk of parathyroid carcinoma by disrupting the CTD of parafibromin.\n <\/jats:p>","DOI":"10.1530\/erc-20-0149","type":"journal-article","created":{"date-parts":[[2020,6,25]],"date-time":"2020-06-25T12:42:39Z","timestamp":1593088959000},"page":"483-494","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":44,"title":["Genotype of CDC73 germline mutation determines risk of parathyroid cancer"],"prefix":"10.1530","volume":"27","author":[{"given":"Yulong","family":"Li","sequence":"first","affiliation":[{"name":"1Division of Endocrinology, Department of Medicine, Penn State University College of Medicine, Hershey, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhua","family":"Zhang","sequence":"additional","affiliation":[{"name":"2Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Poorni R","family":"Adikaram","sequence":"additional","affiliation":[{"name":"2Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Welch","sequence":"additional","affiliation":[{"name":"2Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Guan","sequence":"additional","affiliation":[{"name":"2Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee S","family":"Weinstein","sequence":"additional","affiliation":[{"name":"2Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haobin","family":"Chen","sequence":"additional","affiliation":[{"name":"3Thoracic Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William F","family":"Simonds","sequence":"additional","affiliation":[{"name":"2Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 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\/27\/9\/ERC-20-0149.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/erc.bioscientifica.com\/downloadpdf\/journals\/erc\/27\/9\/ERC-20-0149.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:55:42Z","timestamp":1784555742000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/erc\/article\/27\/9\/483-494\/25529"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9]]},"references-count":0,"journal-issue":{"issue":"9"},"URL":"https:\/\/doi.org\/10.1530\/erc-20-0149","relation":{},"ISSN":["1351-0088","1479-6821"],"issn-type":[{"value":"1351-0088","type":"print"},{"value":"1479-6821","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9]]}}}