{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T16:02:18Z","timestamp":1772035338035,"version":"3.50.1"},"reference-count":68,"publisher":"Bioscientifica","issue":"1","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["etj.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,1,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Paediatric and young adult differentiated thyroid carcinoma (DTC) often presents at an advanced stage but carries an excellent prognosis. While age-related genomic differences from adult DTC are recognized, it remains unclear whether outcomes are driven by age or tumour biology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analysed a multi-institutional cohort of 363 patients aged 0\u201325 years who underwent molecular testing and surgical management. Age was categorized using cut-offs at \u22648, 9\u201314, 15\u201318, and 19\u201325 years. The primary endpoint was disease status at last follow-up, categorized according to American Thyroid Association (ATA) response criteria. Multivariable ordered logistic regression was used to test the independent prognostic effect of somatic driver mutations while adjusting for age, sex, and follow-up duration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Distinct age-related patterns of oncogenic drivers were observed: RET and NTRK1\/3 fusions were predominant in younger patients,\n                      <jats:italic>BRAF<\/jats:italic>\n                      V600E was most frequent in adolescents, and\n                      <jats:italic>RAS<\/jats:italic>\n                      mutations were enriched in young adults. After adjustment, driver mutations independently predicted long-term outcomes.\n                      <jats:italic>NTRK1\/3<\/jats:italic>\n                      fusions (aOR = 5.29, 95% CI: 1.77\u201315.79),\n                      <jats:italic>BRAF<\/jats:italic>\n                      V600E (aOR = 3.45, 95% CI: 1.37\u20138.70), and RET fusions (aOR = 3.34, 95% CI: 1.13\u20139.90) were associated with significantly higher odds of a non-excellent outcome. Conversely,\n                      <jats:italic>RAS<\/jats:italic>\n                      mutations showed a favourable trend, and all\n                      <jats:italic>DICER1<\/jats:italic>\n                      -mutant cases achieved excellent outcomes. While prognosis steadily improved with age, mutation status remained the dominant factor determining outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Somatic drivers offer prognostic insights independent of age in paediatric and young adult DTC, establishing a molecular framework for precision risk stratification that complements traditional clinical staging and age-based assessments.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1530\/etj-25-0310","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T16:43:44Z","timestamp":1767804224000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-16","source":"Crossref","is-referenced-by-count":0,"title":["The influence of age-independent somatic driver alterations on clinical outcomes in paediatric and young adult thyroid cancer"],"prefix":"10.1530","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3736-1323","authenticated-orcid":true,"given":"Sule","family":"Canberk","sequence":"first","affiliation":[{"name":"RISE-Health, Department of Pathology, Faculty of Medicine of The University of Porto, Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0863-7500","authenticated-orcid":true,"given":"Amber","family":"Isaza","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes, Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0629-0160","authenticated-orcid":true,"given":"Mya","family":"Bojarsky","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes, Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA"}]},{"given":"Mariana","family":"Simpl\u00edcio","sequence":"additional","affiliation":[{"name":"RISE-Health, Department of Pathology, Faculty of Medicine of The University of Porto, Porto, Portugal"}]},{"given":"Helena","family":"Barroca","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Anatomia Patol\u00f3gica, Centro Hospitalar Universit\u00e1rio de S Jo\u00e3o, Porto, Portugal"}]},{"given":"Serra Z","family":"Akkoyunlu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey"}]},{"given":"G\u00fcven","family":"G\u00fcnver","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey"}]},{"given":"Isabel","family":"Almeida","sequence":"additional","affiliation":[{"name":"RISE-Health, Department of Pathology, Faculty of Medicine of The University of Porto, Porto, Portugal"}]},{"given":"Filippo","family":"Dello Iacovo","sequence":"additional","affiliation":[{"name":"Department of Public Health, University of Naples Federico II, Naples, Italy"}]},{"given":"Anna M","family":"Carillo","sequence":"additional","affiliation":[{"name":"Department of Public Health, University of Naples Federico II, Naples, Italy"}]},{"given":"Mariantonia","family":"Nacchio","sequence":"additional","affiliation":[{"name":"Department of Public Health, University of Naples Federico II, Naples, Italy"}]},{"given":"Elena","family":"Vigliar","sequence":"additional","affiliation":[{"name":"Department of Public Health, University of Naples Federico II, Naples, Italy"}]},{"given":"Claudio","family":"Bellevicine","sequence":"additional","affiliation":[{"name":"Department of Public Health, University of Naples Federico II, Naples, Italy"}]},{"given":"Giancarlo","family":"Troncone","sequence":"additional","affiliation":[{"name":"Department of Public Health, University of Naples Federico II, Naples, Italy"}]},{"given":"Riley","family":"Larkin","sequence":"additional","affiliation":[{"name":"Pediatric Otolaryngology - Head and Neck Surgery at Vanderbilt Children\u2019s Hospital, Nashville, Tennessee, USA"}]},{"given":"Ryan H","family":"Belcher","sequence":"additional","affiliation":[{"name":"Pediatric Otolaryngology - Head and Neck Surgery at Vanderbilt Children\u2019s Hospital, Nashville, Tennessee, USA"}]},{"given":"Vivian","family":"Weiss","sequence":"additional","affiliation":[{"name":"Pediatric Otolaryngology - Head and Neck Surgery at Vanderbilt Children\u2019s Hospital, Nashville, Tennessee, USA"}]},{"given":"Huiying","family":"Wang","sequence":"additional","affiliation":[{"name":"Pediatric Otolaryngology - Head and Neck Surgery at Vanderbilt Children\u2019s Hospital, Nashville, Tennessee, USA"}]},{"given":"Zubair","family":"Baloch","sequence":"additional","affiliation":[{"name":"Department of Pathology & Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA"}]},{"given":"Fernando","family":"Schmitt","sequence":"additional","affiliation":[{"name":"RISE-Health, Department of Pathology, Faculty of Medicine of The University of Porto, Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3952-881X","authenticated-orcid":true,"given":"Andrew","family":"Bauer","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes, Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA"}]}],"member":"416","reference":[{"key":"bib1","series-title":"J Clin Endocrinol Metab","first-page":"e1683","article-title":"Distant metastases from childhood differentiated thyroid carcinoma: clinical course and mutational landscape","volume":"106","author":"Nies M","year":"2021","unstructured":"Nies M\n, \nVassilopoulou-Sellin R\n, \nBassett RL\n, et al.\n Distant metastases from childhood differentiated thyroid carcinoma: clinical course and mutational landscape. 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(https:\/\/doi.org\/10.1089\/thy.2014.0460)"},{"key":"bib3","series-title":"Endocrinol Metab Clin North Am","first-page":"389","article-title":"Molecular genetics of thyroid cancer in children and adolescents","volume":"46","author":"Bauer AJ","year":"2017","unstructured":"Bauer AJ\n\n. Molecular genetics of thyroid cancer in children and adolescents. Endocrinol Metab Clin North Am 2017 46 389\u2013403. (https:\/\/doi.org\/10.1016\/j.ecl.2017.01.014)"},{"key":"bib4","series-title":"Cancers","first-page":"1549","article-title":"Paediatric thyroid carcinoma: the genetic revolution and its implications for therapy and outcomes","volume":"17","author":"Vanderniet JA","year":"2025","unstructured":"Vanderniet JA\n, \nFuentes-Bolanos NA\n, \nCho YH\n, et al.\n Paediatric thyroid carcinoma: the genetic revolution and its implications for therapy and outcomes. Cancers 2025 17 1549. (https:\/\/doi.org\/10.3390\/cancers17091549)"},{"key":"bib5","series-title":"Endocr Rev","first-page":"397","article-title":"Molecular landscape and therapeutic strategies in pediatric differentiated thyroid carcinoma","volume":"46","author":"Yang AT","year":"2025","unstructured":"Yang AT\n, \nLai ST\n, \nLaetsch TW\n, et al.\n Molecular landscape and therapeutic strategies in pediatric differentiated thyroid carcinoma. Endocr Rev 2025 46 397. (https:\/\/doi.org\/10.1210\/endrev\/bnaf003)"},{"key":"bib6","series-title":"J Clin Investig","article-title":"NTRK and RET fusion-directed therapy in pediatric thyroid cancer yields a tumor response and radioiodine uptake","volume":"131","author":"Lee YA","year":"2021","unstructured":"Lee YA\n, \nLee H\n, \nIm SW\n, et al.\n NTRK and RET fusion-directed therapy in pediatric thyroid cancer yields a tumor response and radioiodine uptake. J Clin Investig 2021 131 e144847. (https:\/\/doi.org\/10.1172\/jci144847)"},{"key":"bib7","series-title":"Thyroid","first-page":"214","article-title":"Prepubertal children with papillary thyroid carcinoma present with more invasive disease than adolescents and young adults","volume":"33","author":"Thiesmeyer JW","year":"2023","unstructured":"Thiesmeyer JW\n, \nEgan CE\n, \nGreenberg JA\n, et al.\n Prepubertal children with papillary thyroid carcinoma present with more invasive disease than adolescents and young adults. Thyroid 2023 33 214\u2013222. 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