{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T23:23:11Z","timestamp":1778196191226,"version":"3.51.4"},"reference-count":47,"publisher":"The Endocrine Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Little is known about the frequency of key mutations in thyroid cancer metastases and its relationship with the primary tumor genotype.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To evaluate the frequency of TERT promoter (TERTp), BRAF, and NRAS mutations in metastatic thyroid carcinomas, analyzing primary thyroid tumors, lymph node metastases (LNMs), and distant metastases.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design and Patients<\/jats:title>\n                  <jats:p>Mutation analysis was performed in 437 tissue samples from 204 patients, mainly with papillary thyroid carcinomas (PTCs; n = 180), including 196 LNMs and 56 distant metastases. All the distant metastases included corresponded to radioiodine-refractory metastatic tissue.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We found the following mutation frequency in primary PTCs, LNMs, and distant metastases, respectively: TERTp: 12.9%, 10.5%, and 52.4%; BRAF: 44.6%, 41.7%, and 23.8%; and NRAS: 1.2%, 1.3%, and 14.3%. There was a significant concordance between the primary tumor genotype and the corresponding LNM for all the genes, in particular BRAF-mutated PTC. The overall concordance between primary tumors and respective distant metastases was low. In the group of patients with PTCs, we found a high frequency of TERTp mutations and a low frequency of BRAF mutations in distant metastases, in comparison with the paired primary tumors. When present in distant metastases, BRAF mutations frequently coexisted with TERTp mutations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>When the genotype of primary tumors is compared with the genotype of LNMs, the concordance is high for all the genes studied. On the other hand, distant metastases show an enrichment in TERTp mutations and a decrease in BRAF mutations. TERTp mutations may play a role in distant metastases.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/jc.2016-2785","type":"journal-article","created":{"date-parts":[[2017,4,19]],"date-time":"2017-04-19T15:09:42Z","timestamp":1492614582000},"page":"1898-1907","source":"Crossref","is-referenced-by-count":114,"title":["TERT, BRAF, and NRAS in Primary Thyroid Cancer and Metastatic Disease"],"prefix":"10.1210","volume":"102","author":[{"given":"Miguel","family":"Melo","sequence":"first","affiliation":[{"name":"i3S Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Porto 4200-135, Portugal"},{"name":"Institute of Molecular Pathology and Immunology, University of Porto, Porto 4200-135, Portugal"},{"name":"Department of Endocrinology, Diabetes, and Metabolism, Centro Hospitalar e Universit\u00e1rio de Coimbra, Coimbra 3000-075, Portugal"},{"name":"Unit of Endocrinology, Faculty of Medicine, University of Coimbra, Coimbra 3000-075, Portugal"}]},{"given":"Adriana","family":"Gaspar da Rocha","sequence":"additional","affiliation":[{"name":"i3S Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Porto 4200-135, Portugal"},{"name":"Institute of Molecular Pathology and Immunology, University of Porto, Porto 4200-135, Portugal"},{"name":"Public Health Unit, ACeS Baixo Mondego, Coimbra 3040-006, Portugal"}]},{"given":"Rui","family":"Batista","sequence":"additional","affiliation":[{"name":"i3S Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Porto 4200-135, Portugal"},{"name":"Institute of Molecular Pathology and Immunology, University of Porto, Porto 4200-135, Portugal"},{"name":"Medical Faculty, University of Porto, Porto 4200-319, Portugal"}]},{"given":"Jo\u00e3o","family":"Vinagre","sequence":"additional","affiliation":[{"name":"i3S Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Porto 4200-135, Portugal"},{"name":"Institute of Molecular Pathology and Immunology, University of Porto, Porto 4200-135, Portugal"},{"name":"Institute of Biomedical Sciences of Abel Salazar, University of Porto, Porto 4050-313, Portugal"}]},{"given":"Maria Jo\u00e3o","family":"Martins","sequence":"additional","affiliation":[{"name":"Department of Pathology, Centro Hospitalar e Universit\u00e1rio de Coimbra, Coimbra 3000-075, Portugal"}]},{"given":"Gracinda","family":"Costa","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Centro Hospitalar e Universit\u00e1rio de Coimbra, Coimbra 3000-075, Portugal"}]},{"given":"Cristina","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes, and Metabolism, Centro Hospitalar e Universit\u00e1rio de Coimbra, Coimbra 3000-075, Portugal"}]},{"given":"Francisco","family":"Carrilho","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes, and Metabolism, Centro Hospitalar e Universit\u00e1rio de Coimbra, Coimbra 3000-075, Portugal"}]},{"given":"Valeriano","family":"Leite","sequence":"additional","affiliation":[{"name":"Unit for Investigation of Molecular Pathobiology, Portuguese Institute of Oncology\u2014Lisbon Center, Lisbon 1099-023, Portugal"},{"name":"Faculty of Medical Sciences, University of Lisbon, Lisbon 1169-056, Portugal"},{"name":"Department of Endocrinology, Portuguese Institute of Oncology\u2014Lisbon Center, Lisbon 1099-023, Portugal"}]},{"given":"Cl\u00e1udia","family":"Lobo","sequence":"additional","affiliation":[{"name":"Department of Pathology, Portuguese Institute of Oncology\u2014Porto Center, Porto 4200-072, Portugal"}]},{"given":"Jos\u00e9 Manuel","family":"Cameselle-Teijeiro","sequence":"additional","affiliation":[{"name":"Department of Pathology, Clinical University Hospital, Servizo Galego de Sa\u00fade (SERGAS), Medical Faculty, University of Santiago de Compostela, Santiago de Compostela 15706, Spain"}]},{"given":"Bruno","family":"Cavadas","sequence":"additional","affiliation":[{"name":"i3S Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Porto 4200-135, Portugal"},{"name":"Institute of Molecular Pathology and Immunology, University of Porto, Porto 4200-135, Portugal"}]},{"given":"Lu\u00edsa","family":"Pereira","sequence":"additional","affiliation":[{"name":"i3S Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Porto 4200-135, Portugal"},{"name":"Institute of Molecular Pathology and Immunology, University of Porto, Porto 4200-135, Portugal"},{"name":"Medical Faculty, University of Porto, Porto 4200-319, Portugal"}]},{"given":"Manuel","family":"Sobrinho-Sim\u00f5es","sequence":"additional","affiliation":[{"name":"i3S Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Porto 4200-135, Portugal"},{"name":"Institute of Molecular Pathology and Immunology, University of Porto, Porto 4200-135, 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