{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T03:59:06Z","timestamp":1789790346354,"version":"4.0.1"},"reference-count":24,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,5]],"date-time":"2021-02-05T00:00:00Z","timestamp":1612483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2014\/06570-6, 2018\/09911-0 and 2018\/26395-5"],"award-info":[{"award-number":["2014\/06570-6, 2018\/09911-0 and 2018\/26395-5"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["304534\/2018-8"],"award-info":[{"award-number":["304534\/2018-8"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["1"],"award-info":[{"award-number":["1"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>The spectrum and incidence of gene fusions in papillary thyroid carcinoma (PTC) can differ significantly depending on the age of onset, histological subtype or radiation exposure history. In sporadic pediatric PTC, RET\/PTC1-3 and AGK-BRAF fusions are common genetic alterations. The role of RET\/PTC as a prognostic marker in pediatric PTC is still under investigation. We recently showed that AGK-BRAF fusion is prevalent in young patients (mean 10 years) and associated with specific and aggressive pathological features such as multifocality and lung metastasis. In this pilot study, we report a unique patient harboring three different foci: the first was positive for AGK-BRAF fusion, the second was positive for just RET\/PTC3 fusion and the third was negative for both rearrangements. To investigate whether AGK-BRAF and RET\/PTC3 are associated with genomic instability and chromatin modifications, we performed quantitative fluorescence in situ hybridization (Q-FISH) of telomere repeats followed by 3D imaging analysis and 3D super-resolution Structured Illumination Microscopy (3D-SIM) to analyze the DNA structure from the foci. We demonstrated in this preliminary study that AGK-BRAF is likely associated with higher levels of telomere-related genomic instability and chromatin remodeling in comparison with RET\/PTC3 foci. Our results suggest a progressive disruption in chromatin structure in AGK-BRAF-positive cells, which might explain a more aggressive disease outcome in patients harboring this rearrangement.<\/jats:p>","DOI":"10.3390\/biology10020125","type":"journal-article","created":{"date-parts":[[2021,2,5]],"date-time":"2021-02-05T08:33:48Z","timestamp":1612514028000},"page":"125","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A Multifocal Pediatric Papillary Thyroid Carcinoma (PTC) Harboring the AGK-BRAF and RET\/PTC3 Fusion in a Mutually Exclusive Pattern Reveals Distinct Levels of Genomic Instability and Nuclear Organization"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7452-5756","authenticated-orcid":false,"given":"Luiza","family":"Sisdelli","sequence":"first","affiliation":[{"name":"The Genetic Basis of Thyroid Tumors Lab, Division of Genetics, Department of Morphology and Genetics, Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo 04039-032, Brazil"},{"name":"Cell Biology, Research Institute of Oncology and Hematology, University of Manitoba, CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Isabel V.","family":"Cordioli","sequence":"additional","affiliation":[{"name":"The Genetic Basis of Thyroid Tumors Lab, Division of Genetics, Department of Morphology and Genetics, Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo 04039-032, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda","family":"Vaisman","sequence":"additional","affiliation":[{"name":"Instituto Nacional do C\u00e2ncer, Rio de Janeiro 22451-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osmar","family":"Monte","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Irmandade da Santa Casa de Miseric\u00f3rdia de S\u00e3o Paulo, S\u00e3o Paulo 01221-010, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos A.","family":"Longui","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Irmandade da Santa Casa de Miseric\u00f3rdia de S\u00e3o Paulo, S\u00e3o Paulo 01221-010, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriano N.","family":"Cury","sequence":"additional","affiliation":[{"name":"Department of Medicine, Irmandade da Santa Casa de Miseric\u00f3rdia de S\u00e3o Paulo, S\u00e3o Paulo 01221-010, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique O.","family":"Freitas","sequence":"additional","affiliation":[{"name":"Medical Genetics Service of the Martag\u00e3o Gesteira Childcare and Pediatrics Institute (IPPMG), Medical School, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-912, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline","family":"Rangel-Pozzo","sequence":"additional","affiliation":[{"name":"Cell Biology, Research Institute of Oncology and Hematology, University of Manitoba, CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5797-2201","authenticated-orcid":false,"given":"Sabine","family":"Mai","sequence":"additional","affiliation":[{"name":"Cell Biology, Research Institute of Oncology and Hematology, University of Manitoba, CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0156-8274","authenticated-orcid":false,"given":"Janete M.","family":"Cerutti","sequence":"additional","affiliation":[{"name":"The Genetic Basis of Thyroid Tumors Lab, Division of Genetics, Department of Morphology and Genetics, Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo 04039-032, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Paulson, V.A., Rudzinski, E.R., and Hawkins, D.S. 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