{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:41:16Z","timestamp":1785404476082,"version":"3.56.0"},"reference-count":0,"publisher":"Bioscientifica","issue":"1","content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,3]]},"abstract":"<jats:p>\n                    The tumor suppressor\n                    <jats:italic>HRPT2<\/jats:italic>\n                    \/\n                    <jats:italic>CDC73<\/jats:italic>\n                    is mutated in constitutive DNA from patients with the familial disorder hyperparathyroidism\u2013jaw tumor syndrome and in \u223c70% of all parathyroid carcinomas. In a number of\n                    <jats:italic>HRPT2<\/jats:italic>\n                    mutant tumors however, expression of the encoded protein parafibromin is lost in the absence of a clear second event such as\n                    <jats:italic>HRPT2<\/jats:italic>\n                    allelic loss or the presence of a second mutation in this tumor suppressor gene. We sought to determine whether hypermethylation of a 713\u200abp CpG island extending 648 nucleotides upstream of the\n                    <jats:italic>HRPT2<\/jats:italic>\n                    translational start site and 65 nucleotides into exon 1 might be a mechanism contributing to the loss of expression of parafibromin in parathyroid tumors. Furthermore, we asked whether mutations might be present in the 5\u2032-untranslated region (5\u2032-UTR) of\n                    <jats:italic>HRPT2<\/jats:italic>\n                    . We investigated a pool of tissue from 3 normal parathyroid glands, as well as 15 individual parathyroid tumor samples including 6 tumors with known\n                    <jats:italic>HRPT2<\/jats:italic>\n                    mutations, for hypermethylation of the\n                    <jats:italic>HRPT2<\/jats:italic>\n                    CpG island. Methylation was not identified in any specimens despite complete loss of parafibromin expression in two parathyroid carcinomas with a single detectable\n                    <jats:italic>HRPT2<\/jats:italic>\n                    mutation and retention of the wild-type\n                    <jats:italic>HRPT2<\/jats:italic>\n                    allele. Furthermore, no mutations of a likely pathogenic nature were identified in the 5\u2032-UTR of\n                    <jats:italic>HRPT2<\/jats:italic>\n                    . These data strongly suggest that alternative mechanisms such as mutation in\n                    <jats:italic>HRPT2<\/jats:italic>\n                    intronic regions, additional epigenetic regulation such as histone modifications, or other regulatory inactivation mechanisms such as targeting by microRNAs may play a role in the loss of parafibromin expression.\n                  <\/jats:p>","DOI":"10.1677\/erc-09-0291","type":"journal-article","created":{"date-parts":[[2009,12,21]],"date-time":"2009-12-21T21:49:38Z","timestamp":1261432178000},"page":"273-282","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":30,"title":["CDC73\/HRPT2 CpG island hypermethylation and mutation of 5\u2032-untranslated sequence are uncommon mechanisms of silencing parafibromin in parathyroid tumors"],"prefix":"10.1530","volume":"17","author":[{"given":"Michael A","family":"Hahn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viive M","family":"Howell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J","family":"Gill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adele","family":"Clarkson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham","family":"Weaire-Buchanan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce G","family":"Robinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leigh","family":"Delbridge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Gimm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang D","family":"Schmitt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin T","family":"Teh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah J","family":"Marsh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","container-title":["Endocrine-Related Cancer"],"original-title":[],"link":[{"URL":"https:\/\/erc.bioscientifica.com\/view\/journals\/erc\/17\/1\/273.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/erc.bioscientifica.com\/downloadpdf\/journals\/erc\/17\/1\/273.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:52:42Z","timestamp":1784555562000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/erc\/article\/17\/1\/273-282\/34750"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,3]]},"references-count":0,"journal-issue":{"issue":"1"},"URL":"https:\/\/doi.org\/10.1677\/erc-09-0291","relation":{},"ISSN":["1351-0088","1479-6821"],"issn-type":[{"value":"1351-0088","type":"print"},{"value":"1479-6821","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,3]]}}}