{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T19:35:32Z","timestamp":1787686532770,"version":"build-2784847793"},"reference-count":41,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2016,1,19]],"date-time":"2016-01-19T00:00:00Z","timestamp":1453161600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"The authors' intradepartmental funding"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>An increase in thyroid cancers, predominantly papillary thyroid carcinoma (PTC), has been recently reported in children.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>The histopathology of 28 consecutive PTCs from the northeast United States was reviewed. None of the patients (ages 6\u201018 years; 20 females, 8 males) had significant exposure to radiation. Nucleic acid from tumors was tested for genetic abnormalities (n = 27). Negative results were reevaluated by targeted next\u2010generation sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Seven of 27 PTCs (26%) had neurotrophic tyrosine kinase receptor (<jats:italic>NTRK<\/jats:italic>) fusion oncogenes (<jats:italic>NTRK<\/jats:italic> type 3\/ets variant 6 [<jats:italic>NTRK3<\/jats:italic>\/<jats:italic>ETV6<\/jats:italic>], n =5; <jats:italic>NTRK3<\/jats:italic>\/unknown, n = 1; and <jats:italic>NTRK<\/jats:italic> type 1\/translocated promoter region, nuclear basket protein [<jats:italic>NTRK1\/TPR<\/jats:italic>], n = 1), including 5 tumors that measured &gt;2 cm and 3 that diffusely involved the entire thyroid or lobe. All 7 tumors had lymphatic invasion, and 5 had vascular invasion. Six of 27 PTCs (22%) had ret proto\u2010oncogene (<jats:italic>RET<\/jats:italic>) fusions (<jats:italic>RET\/PTC1<\/jats:italic>, n = 5; <jats:italic>RET\/PTC3<\/jats:italic>, n = 1); 2 tumors measured &gt;2 cm and diffusely involved the thyroid, and 5 had lymphatic invasion, with vascular invasion in 2. Thirteen PTCs had the B\u2010Raf proto\u2010oncogene, serine\/threonine kinase (BRAF) valine\u2010to\u2010glutamic acid mutation at position 600 (<jats:italic>BRAF<jats:sup>V<\/jats:sup><\/jats:italic><jats:sup>600E<\/jats:sup>) (13 of 27 tumors; 48%), 11 measured &lt;2 cm, and 6 had lymphatic invasion (46%), with vascular invasion in 3. Fusion oncogene tumors, compared with <jats:italic>BRAF<jats:sup>V<\/jats:sup><\/jats:italic><jats:sup>600E<\/jats:sup> PTCs, were associated with large size (mean, 2.2 cm vs 1.5 cm, respectively; <jats:italic>P<\/jats:italic> = .05), solid and diffuse variants (11 of 13 vs 0 of 13 tumors, respectively; <jats:italic>P<\/jats:italic> &lt; .001), and lymphovascular invasion (12 of 13 vs 6 of 13 tumors, respectively; <jats:italic>P<\/jats:italic> = .02); <jats:italic>BRAF<jats:sup>V<\/jats:sup><\/jats:italic><jats:sup>600E<\/jats:sup> PTCs were predominantly the classic variant (12 of 13 vs 1 of 13 tumors). Two tumors metastasized to the lung, and both had fusion oncogenes (<jats:italic>NTRK1\/TPR<\/jats:italic>, n = 1; <jats:italic>RET\/PTC1<\/jats:italic>, n = 1).<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Fusion oncogene PTC presents with more extensive disease and aggressive pathology than <jats:italic>BRAF<jats:sup>V<\/jats:sup><\/jats:italic><jats:sup>600E<\/jats:sup> PTC in the pediatric population. The high prevalence of the <jats:italic>NTRK1\/NTRK3<\/jats:italic> fusion oncogene PTCs in the United States is unusual and needs further investigation. <jats:bold><jats:italic>Cancer<\/jats:italic> 2016;122:1097\u20131107.<\/jats:bold> \u00a9 <jats:italic>2016 American Cancer Society<\/jats:italic><\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.29887","type":"journal-article","created":{"date-parts":[[2016,1,19]],"date-time":"2016-01-19T13:58:14Z","timestamp":1453211894000},"page":"1097-1107","source":"Crossref","is-referenced-by-count":224,"title":["<i>NTRK<\/i> fusion oncogenes in pediatric papillary thyroid carcinoma in northeast United States"],"prefix":"10.1002","volume":"122","author":[{"given":"Manju L.","family":"Prasad","sequence":"first","affiliation":[{"name":"Department of Pathology Yale School of Medicine New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Vyas","sequence":"additional","affiliation":[{"name":"Department 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