{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T03:43:09Z","timestamp":1767066189433,"version":"3.40.5"},"reference-count":29,"publisher":"Bioscientifica","issue":"9","license":[{"start":{"date-parts":[[2023,7,6]],"date-time":"2023-07-06T00:00:00Z","timestamp":1688601600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ec.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,8,2]]},"abstract":"<jats:p>Nineteen cases of parathyroid carcinoma in patients with multiple endocrine neoplasia type 1 have been reported in the literature, of which 11 carry an inactivating germline mutation in the <jats:italic>MEN1<\/jats:italic> gene. Somatic genetic abnormalities in these parathyroid carcinomas have never been detected. In this paper, we aimed to describe the clinical and molecular characterization of a parathyroid carcinoma identified in a patient with MEN1. A 60-year-old man was diagnosed with primary hyperparathyroidism during the postoperative period of lung carcinoid surgery. Serum calcium and parathyroid hormone levels were 15.0 mg\/dL (8.4\u201310.2) and 472 pg\/mL (12\u201365), respectively. The patient underwent parathyroid surgery, and histological findings were consistent with parathyroid carcinoma. Analysis of the <jats:italic>MEN1<\/jats:italic> gene by next-generation sequencing (NGS) identified a novel germline heterozygous nonsense pathogenic variant (c.978C&gt;A; p.(Tyr326*)), predicted to encode a truncated protein. Genetic analysis of the parathyroid carcinoma revealed a c.307del, p.(Leu103Cysfs*16) frameshift truncating somatic <jats:italic>MEN1<\/jats:italic> variant in the <jats:italic>MEN1<\/jats:italic> gene, which is consistent with <jats:italic>MEN1<\/jats:italic> tumor-suppressor role, confirming its involvement in parathyroid carcinoma etiology. Genetic analysis of <jats:italic>CDC73<\/jats:italic>, <jats:italic>GCM2<\/jats:italic>, <jats:italic>TP53<\/jats:italic>, <jats:italic>RB1<\/jats:italic>, <jats:italic>AKT1<\/jats:italic>, <jats:italic>MTOR<\/jats:italic>, <jats:italic>PIK3CA<\/jats:italic> and <jats:italic>CCND1<\/jats:italic> genes in the parathyroid carcinoma DNA did not detect any somatic mutations. To our knowledge, this is the first report of a PC case presenting both germline (first-hit) and somatic (second-hit) inactivation of the <jats:italic>MEN1<\/jats:italic> gene.<\/jats:p>","DOI":"10.1530\/ec-22-0479","type":"journal-article","created":{"date-parts":[[2023,7,6]],"date-time":"2023-07-06T14:47:44Z","timestamp":1688654864000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-10","source":"Crossref","is-referenced-by-count":4,"title":["Clinical and molecular characterization of parathyroid carcinoma in multiple endocrine neoplasia type 1"],"prefix":"10.1530","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0481-8494","authenticated-orcid":true,"given":"Sara","family":"Lomelino Pinheiro","sequence":"first","affiliation":[{"name":"Servi\u00e7o de Endocrinologia, Instituto Portugu\u00eas de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9249-3206","authenticated-orcid":true,"given":"Ana","family":"Saramago","sequence":"additional","affiliation":[{"name":"Unidade de Investiga\u00e7\u00e3o em Patobiologia Molecular, Instituto Portugu\u00eas de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8946-8635","authenticated-orcid":true,"given":"Branca Maria","family":"Cavaco","sequence":"additional","affiliation":[{"name":"Unidade de Investiga\u00e7\u00e3o em Patobiologia Molecular, Instituto Portugu\u00eas de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7901-7600","authenticated-orcid":true,"given":"Carmo","family":"Martins","sequence":"additional","affiliation":[{"name":"Unidade de Investiga\u00e7\u00e3o em Patobiologia Molecular, Instituto Portugu\u00eas de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5479-7332","authenticated-orcid":true,"given":"Valeriano","family":"Leite","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Endocrinologia e Unidade de Investiga\u00e7\u00e3o em Patobiologia Molecular, Instituto Portugu\u00eas de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1958-4531","authenticated-orcid":true,"given":"Tiago","family":"Nunes da Silva","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Endocrinologia e Unidade de Investiga\u00e7\u00e3o em Patobiologia Molecular, Instituto Portugu\u00eas de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Frontiers of Hormone Research","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1159\/000491039","article-title":"Parathyroid carcinoma","volume":"51","author":"Cetani","year":"2019","unstructured":"Cetani FPardi E & Marcocci C. 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