{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T17:45:38Z","timestamp":1763747138136},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"2","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,2]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Primary hyperparathyroidism (pHPT) is characterised by an inappropriate over production of parathyroid hormone and it is the most frequent pathological condition of the parathyroid glands. A minority of the cases belong to familial forms, but most of them are sporadic. The genetic alterations underlying the sporadic forms of pHPT remain poorly understood. The main goal of our study is to perform the molecular characterisation of a series of sporadic pHPT cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design and methods<\/jats:title><jats:p>We have studied matched blood and tumour from 24 patients with pHPT, who went to a medical appointment in Hospital Pedro Hispano. Informed consent was obtained from all individuals. The<jats:italic>MEN1<\/jats:italic>,<jats:italic>RET<\/jats:italic>and<jats:italic>CDKN1B<\/jats:italic>molecular study was carried out in the germline DNA by PCR\/SSCP and direct sequencing. Parathyroid tumours were further analysed by the same methods for<jats:italic>MEN1<\/jats:italic>,<jats:italic>CDKN1B<\/jats:italic>and<jats:italic>CTNNB1<\/jats:italic>genetic alterations. The multiplex ligation-dependent probe amplification technique enabled the evaluation of<jats:italic>MEN1<\/jats:italic>gene deletions. Protein expression for menin, cyclin D1, parafibromin, p27<jats:sup>Kip1<\/jats:sup>, \u03b2-catenin and Ki-67 was conducted by immunohistochemistry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The study of parathyroid tumours detected two somatic<jats:italic>MEN1<\/jats:italic>mutations (c.249_252delGTCT and c.115_163del49bp) and revealed the presence of<jats:italic>MEN1<\/jats:italic>intragenic deletions in 54% (13\/24) of the tumours. In<jats:italic>RET<\/jats:italic>and<jats:italic>CDKN1B<\/jats:italic>genes only previously described, non-pathogenic variants were found. Cyclin D1 protein was overexpressed in 13% (3\/24) of tumours.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results suggest that<jats:italic>MEN1<\/jats:italic>alterations, remarkably intragenic deletions, may represent the most prevalent genetic alteration in sporadic parathyroid tumours.<\/jats:p><\/jats:sec>","DOI":"10.1530\/eje-12-0327","type":"journal-article","created":{"date-parts":[[2012,10,24]],"date-time":"2012-10-24T05:30:14Z","timestamp":1351056614000},"page":"119-128","update-policy":"http:\/\/dx.doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":28,"title":["MEN1 intragenic deletions may represent the most prevalent somatic event in sporadic primary hyperparathyroidism"],"prefix":"10.1093","volume":"168","author":[{"given":"Maria In\u00eas","family":"Alvelos","sequence":"first","affiliation":[]},{"given":"Jo\u00e3o","family":"Vinagre","sequence":"additional","affiliation":[]},{"given":"Elsa","family":"Fonseca","sequence":"additional","affiliation":[]},{"given":"Eva","family":"Barbosa","sequence":"additional","affiliation":[]},{"given":"Jos\u00e9","family":"Teixeira-Gomes","sequence":"additional","affiliation":[]},{"given":"Manuel","family":"Sobrinho-Sim\u00f5es","sequence":"additional","affiliation":[]},{"given":"Paula","family":"Soares","sequence":"additional","affiliation":[]}],"member":"286","reference":[{"key":"1_29293733","first-page":"N68","volume":"17","year":"2002","journal-title":"Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research","ISSN":"http:\/\/id.crossref.org\/issn\/0884-0431","issn-type":"print"},{"key":"2_44791175","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.5858\/2009-0578-CCR.1","volume":"134","year":"2010","journal-title":"ARCHIVES OF PATHOLOGY LABORATORY MEDICINE"},{"issue":"11","key":"3_18724472","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1007\/BF03345303","volume":"27","author":"Scarpelli","year":"2004","journal-title":"Journal of endocrinological investigation","ISSN":"http:\/\/id.crossref.org\/issn\/0391-4097","issn-type":"print"},{"issue":"10","key":"4_4408973","doi-asserted-by":"publisher","first-page":"966","DOI":"10.1136\/jcp.30.10.966","volume":"30","author":"Dinnen","year":"1977","journal-title":"Journal of Clinical Pathology","ISSN":"http:\/\/id.crossref.org\/issn\/0021-9746","issn-type":"print"},{"issue":"42","key":"5_22774905","doi-asserted-by":"publisher","first-page":"15558","DOI":"10.1073\/pnas.0603877103","volume":"103","year":"2006","journal-title":"PNAS","ISSN":"http:\/\/id.crossref.org\/issn\/0027-8424","issn-type":"print"},{"issue":"1","key":"6_38458622","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1159\/000320366","volume":"93","author":"Marinoni","year":"2011","journal-title":"Neuroendocrinology","ISSN":"http:\/\/id.crossref.org\/issn\/0028-3835","issn-type":"print"},{"key":"7_44791176","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.beem.2010.01.001","volume":"24","year":"2010","journal-title":"BEST PRACTICE RESEARCH CLINICAL ENDOCRINOLOGY METABOLISM"},{"issue":"3","key":"8_41342294","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1530\/EJE-11-0929","volume":"166","year":"2012","journal-title":"European Journal of Endocrinology","ISSN":"http:\/\/id.crossref.org\/issn\/0804-4643","issn-type":"print"},{"issue":"10","key":"9_16447327","doi-asserted-by":"publisher","first-page":"3663","DOI":"10.1210\/jc.81.10.3663","volume":"81","author":"Tahara","year":"1996","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"http:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"issue":"10","key":"10_6377389","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1046\/j.1440-1827.1999.00961.x","volume":"49","author":"Kishikawa","year":"1999","journal-title":"Pathology international","ISSN":"http:\/\/id.crossref.org\/issn\/1320-5463","issn-type":"print"},{"issue":"1","key":"11_17654312","first-page":"1","volume":"1653","author":"Giles","year":"2003","journal-title":"Biochimica et Biophysica Acta. 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