{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T14:08:22Z","timestamp":1774534102661,"version":"3.50.1"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T00:00:00Z","timestamp":1721347200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T00:00:00Z","timestamp":1721347200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Foundation for Science and Technology, Portugal","award":["2022.05763.PTDC"],"award-info":[{"award-number":["2022.05763.PTDC"]}]},{"name":"Foundation for Science and Technology, Portugal","award":["2022.05763.PTDC"],"award-info":[{"award-number":["2022.05763.PTDC"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Endocrine"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>To perform a molecular profiling of the metastases from papillary thyroid carcinomas (PTCs) and poorly differentiated thyroid carcinomas (PDTCs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrieved and analyzed the molecular and clinical features of 136 metastases from PTCs and 35 metastases from PDTCs subjected to targeted DNA sequencing, from cBioPortal. The clinicopathological data included the number and location of the metastases, and genomic data included mutations, translocations, copy number alterations and fraction of the genome altered (FGA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Bone metastases from PTCs had a lower frequency of\n                      <jats:italic>BRAF<\/jats:italic>\n                      mutations than the lymph node metastases (LNMs) (43% vs 88%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01), and a higher frequency of\n                      <jats:italic>RBM10<\/jats:italic>\n                      and\n                      <jats:italic>NRAS<\/jats:italic>\n                      mutations than the LNMs (21% vs 3% for both,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). The FGA of the bone metastases was higher than the FGA of the lung metastases (5.6% vs 1.3%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). The frequency of\n                      <jats:italic>RET<\/jats:italic>\n                      translocations was higher in the lung metastases from PTCs than the LNMs (15% vs 3%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). The LNMs from PTC patients harboring 4 or more distant metastases (DMs) had a higher frequency of\n                      <jats:italic>TERT<\/jats:italic>\n                      promoter mutations than the LNMs from patients harboring less than 4 DMs (96% vs 65%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001).\n                      <jats:italic>SDHA<\/jats:italic>\n                      gene amplifications were enriched in the bone metastases from PDTCs and absent in the LNMs (38% vs 0%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Metastases from PTCs and PDTCs harbor clinically relevant alterations affecting distinct body locations, such as\n                      <jats:italic>NRAS<\/jats:italic>\n                      and\n                      <jats:italic>RBM10<\/jats:italic>\n                      mutations,\n                      <jats:italic>RET<\/jats:italic>\n                      translocations and\n                      <jats:italic>SDHA<\/jats:italic>\n                      amplifications that may be explored therapeutically.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s12020-024-03968-0","type":"journal-article","created":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T16:19:26Z","timestamp":1721405966000},"page":"505-509","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Genomic profiling of lymph node and distant metastases from papillary and poorly differentiated thyroid carcinomas"],"prefix":"10.1007","volume":"86","author":[{"given":"Valdemar","family":"M\u00e1ximo","sequence":"first","affiliation":[]},{"given":"Miguel","family":"Melo","sequence":"additional","affiliation":[]},{"given":"Manuel","family":"Sobrinho-Sim\u00f5es","sequence":"additional","affiliation":[]},{"given":"Paula","family":"Soares","sequence":"additional","affiliation":[]},{"given":"Arnaud","family":"Da Cruz Paula","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2024,7,19]]},"reference":[{"key":"3968_CR1","doi-asserted-by":"publisher","first-page":"6194","DOI":"10.3390\/cancers13246194","volume":"13","author":"P Mishra","year":"2021","unstructured":"P. Mishra, D. Laha, R. Grant, N. Nilubol, Advances in Biomarker-Driven Targeted Therapies in Thyroid Cancer. Cancers 13, 6194 (2021). https:\/\/doi.org\/10.3390\/cancers13246194","journal-title":"Cancers"},{"key":"3968_CR2","doi-asserted-by":"publisher","first-page":"e230144","DOI":"10.1530\/ERC-23-0144","volume":"31","author":"V M\u00e1ximo","year":"2024","unstructured":"V. M\u00e1ximo et al. Genomic profiling of primary and metastatic thyroid carcinomas. Endocr. Relat. Cancer 31, e230144 (2024). https:\/\/doi.org\/10.1530\/ERC-23-0144","journal-title":"Endocr. Relat. Cancer"},{"key":"3968_CR3","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.1057532","volume":"12","author":"Y Fang","year":"2023","unstructured":"Y. Fang et al. Genetic and clinical profiles of 160 papillary thyroid cancers with lateral neck lymph node metastasis. Front Oncol. 12, 1057532 (2023). https:\/\/doi.org\/10.3389\/fonc.2022.1057532","journal-title":"Front Oncol."},{"key":"3968_CR4","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1530\/ERC-19-0452","volume":"27","author":"E Song","year":"2020","unstructured":"E. Song et al. Genetic profile of advanced thyroid cancers in relation to distant metastasis. Endocr. Relat. Cancer 27, 285\u2013293 (2020). https:\/\/doi.org\/10.1530\/ERC-19-0452","journal-title":"Endocr. Relat. Cancer"},{"key":"3968_CR5","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1016\/j.cell.2022.01.003","volume":"185","author":"B Nguyen","year":"2022","unstructured":"B. Nguyen et al. Genomic characterization of metastatic patterns from prospective clinical sequencing of 25,000 patients. Cell 185, 563\u2013575 (2022). https:\/\/doi.org\/10.1016\/j.cell.2022.01.003","journal-title":"Cell"},{"key":"3968_CR6","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1038\/nm.4333","volume":"23","author":"A Zehir","year":"2017","unstructured":"A. Zehir et al. Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients. Nat. Med. 23, 703\u2013713 (2017). https:\/\/doi.org\/10.1038\/nm.4333","journal-title":"Nat. Med."},{"key":"3968_CR7","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/j.ygyno.2021.02.015","volume":"161","author":"A Da Cruz Paula","year":"2021","unstructured":"A. Da Cruz Paula et al. Genetic and molecular subtype heterogeneity in newly diagnosed early- and advanced-stage endometrial cancer. Gynecol. Oncol. 161, 535\u2013544 (2021). https:\/\/doi.org\/10.1016\/j.ygyno.2021.02.015","journal-title":"Gynecol. Oncol."},{"key":"3968_CR8","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13806-x","volume":"11","author":"SH Kim","year":"2020","unstructured":"S.H. Kim et al. Identification of recurrent FHL2-GLI2 oncogenic fusion in sclerosing stromal tumors of the ovary. Nat. Commun. 11, 44 (2020). https:\/\/doi.org\/10.1038\/s41467-019-13806-x","journal-title":"Nat. Commun."},{"key":"3968_CR9","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/s13000-016-0458-6","volume":"11","author":"JS Bae","year":"2016","unstructured":"J.S. Bae et al. Clinical utility of TERT promoter mutations and ALK rearrangement in thyroid cancer patients with a high prevalence of BRAF V600E mutation. Diagn. Pathol. 11, 21 (2016). https:\/\/doi.org\/10.1186\/s13000-016-0458-6","journal-title":"Diagn. Pathol."},{"key":"3968_CR10","doi-asserted-by":"publisher","first-page":"E1745","DOI":"10.1210\/c.2012-1526","volume":"9","author":"V Sancisi","year":"2012","unstructured":"V. Sancisi, D. Nicoli, M. Ragazzi, S. Piana, A. Ciarrocchi, BRAFV600E mutation does not mean distant metastasis in thyroid papillary carcinomas. J. Clin. Endocrinol. Metab. 9, E1745\u2013E1749 (2012). https:\/\/doi.org\/10.1210\/c.2012-1526","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"3968_CR11","doi-asserted-by":"publisher","first-page":"2186","DOI":"10.3892\/ol.2017.6395","volume":"2","author":"F Pani","year":"2017","unstructured":"F. Pani et al. Aggressive differentiated thyroid cancer with multiple metastases and NRAS and TERT promoter mutations: a case report. Oncol. Lett. 2, 2186\u20132190 (2017). https:\/\/doi.org\/10.3892\/ol.2017.6395","journal-title":"Oncol. Lett."},{"key":"3968_CR12","doi-asserted-by":"publisher","first-page":"1988","DOI":"10.1158\/1078-0432.CCR-16-1679","volume":"8","author":"S Kato","year":"2017","unstructured":"S. Kato et al. Ret aberrations in diverse cancers: next-generation sequencing of 4,8171 patients. Clin. Cancer Res. 8, 1988\u20131997 (2017)","journal-title":"Clin. Cancer Res."},{"key":"3968_CR13","doi-asserted-by":"publisher","first-page":"1132","DOI":"10.3390\/jpm13071132","volume":"7","author":"R Martins","year":"2023","unstructured":"R. Martins, T.L. Jesus, L. Cardoso, P. Soares, J. Vinagre, Personalized medicine in medullary thyroid carcinoma: a broad review of emerging treatments. J. Pers. Med. 7, 1132 (2023). https:\/\/doi.org\/10.3390\/jpm13071132","journal-title":"J. Pers. Med."},{"key":"3968_CR14","doi-asserted-by":"publisher","first-page":"1898","DOI":"10.1210\/jc.2016-2785","volume":"102","author":"M Melo","year":"2017","unstructured":"M. Melo et al. TERT, BRAF, and NRAS in Primary Thyroid Cancer and Metastatic Disease. J. Clin. Endocrinol. Metab. 102, 1898\u20131907 (2017). https:\/\/doi.org\/10.1210\/jc.2016-2785","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"3968_CR15","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1089\/thy.2014.0241","volume":"25","author":"K Pak","year":"2014","unstructured":"K. Pak, S. Suh, S.K. Kim, I.J. Kim, Prognostic value of genetic mutations in thyroid cancer: a meta-analysis. Thyroid 25, 63\u201370 (2014). https:\/\/doi.org\/10.1089\/thy.2014.0241","journal-title":"Thyroid"},{"key":"3968_CR16","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10680-5","volume":"10","author":"SK Yoo","year":"2019","unstructured":"S.K. Yoo et al. Integrative analysis of genomic and transcriptomic characteristics associated with progression of aggressive thyroid cancer. Nat. Commun. 10, 2764 (2019). https:\/\/doi.org\/10.1038\/s41467-019-10680-5","journal-title":"Nat. Commun."},{"key":"3968_CR17","doi-asserted-by":"publisher","first-page":"3059","DOI":"10.1158\/1078-0432.CCR-18-0373","volume":"13","author":"N Pozdeyev","year":"2018","unstructured":"N. Pozdeyev, L.M. Gay, E.S. Sokol et al. Genetic analysis of 779 advanced differentiated and anaplastic thyroid cancers. Clin. Cancer Res. 13, 3059\u20133068 (2018). https:\/\/doi.org\/10.1158\/1078-0432.CCR-18-0373","journal-title":"Clin. Cancer Res."},{"key":"3968_CR18","doi-asserted-by":"publisher","first-page":"1575","DOI":"10.1158\/1535-7163.MCT-17-0871","volume":"7","author":"H Chen","year":"2018","unstructured":"H. Chen et al. Molecular profile of advanced thyroid carcinomas by next-generation sequencing: characterizing tumors beyond diagnosis for targeted therapy. Mol. Cancer Ther. 7, 1575\u20131584 (2018). https:\/\/doi.org\/10.1158\/1535-7163.MCT-17-0871","journal-title":"Mol. Cancer Ther."},{"key":"3968_CR19","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.ygyno.2023.10.007","volume":"179","author":"AM Praiss","year":"2023","unstructured":"A.M. Praiss et al. TERT promoter mutations and gene amplifications in endometrial cancer. Gynecol. Oncol. 179, 16\u201323 (2023). https:\/\/doi.org\/10.1016\/j.ygyno.2023.10.007","journal-title":"Gynecol. Oncol."},{"key":"3968_CR20","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1158\/1538-7445.AM2023-7","volume":"83","author":"L Wang","year":"2023","unstructured":"L. Wang et al. Exploiting metabolic vulnerabilities of ovarian cancer with upregulated succinate dehydrogenase. Cancer Res. 83, 7 (2023)","journal-title":"Cancer Res."}],"container-title":["Endocrine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12020-024-03968-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12020-024-03968-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12020-024-03968-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,23]],"date-time":"2024-11-23T04:16:32Z","timestamp":1732335392000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12020-024-03968-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,19]]},"references-count":20,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["3968"],"URL":"https:\/\/doi.org\/10.1007\/s12020-024-03968-0","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-4528308\/v1","asserted-by":"object"}]},"ISSN":["1559-0100"],"issn-type":[{"value":"1559-0100","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,19]]},"assertion":[{"value":"4 June 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 July 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 July 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"M.M. participated in advisory board meetings organized by Eisai Co. and Elli Lilly and Company. The remaining authors have no disclosures to declare.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}