{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T11:43:29Z","timestamp":1791546209073,"version":"4.3.4"},"reference-count":42,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,12,10]],"date-time":"2013-12-10T00:00:00Z","timestamp":1386633600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001677","name":"Institut national de la sant\u00e9 et de la recherche m\u00e9dicale","doi-asserted-by":"publisher","award":["CA88041"],"award-info":[{"award-number":["CA88041"]}],"id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2014,3,15]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>In their previous analysis of papillary thyroid carcinomas (PTCs) from an Ukrainian\u2010American cohort that was exposed to iodine\u2010131 (<jats:sup>131<\/jats:sup>I) from the Chernobyl accident, the authors identified <jats:italic>RET\/PTC<\/jats:italic> rearrangements and other driver mutations in 60% of tumors.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>In this study, the remaining mutation\u2010negative tumors from that cohort were analyzed using RNA sequencing (RNA\u2010Seq) and reverse transcriptase\u2010polymerase chain reaction to identify novel chromosomal rearrangements and to characterize their relation with radiation dose.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>The ETS variant gene 6 (<jats:italic>ETV6<\/jats:italic>)\u2010neurotrophin receptor 3 (<jats:italic>NTRK3<\/jats:italic>) rearrangement (<jats:italic>ETV6<\/jats:italic>\u2010<jats:italic>NTRK3<\/jats:italic>) was identified by RNA\u2010Seq in a tumor from a patient who received a high <jats:sup>131<\/jats:sup>I dose. Overall, the rearrangement was detected in 9 of 62 (14.5%) post\u2010Chernobyl PTCs and in 3 of 151 (2%) sporadic PTCs (<jats:italic>P<\/jats:italic>\u2009=\u2009.019). The most common fusion type was between exon 4 of <jats:italic>ETV6<\/jats:italic> and exon 14 of <jats:italic>NTRK3<\/jats:italic>. The prevalence of <jats:italic>ETV6\u2010NTRK3<\/jats:italic> rearrangement in post\u2010Chernobyl PTCs was associated with increasing <jats:sup>131<\/jats:sup>I dose, albeit at borderline significance (<jats:italic>P<\/jats:italic>\u2009=\u2009.126). The group of rearrangement\u2010positive PTCs (<jats:italic>ETV6\u2010NTRK3<\/jats:italic>, <jats:italic>RET\/PTC<\/jats:italic>, <jats:italic>PAX8\u2010PPAR\u03b3<\/jats:italic>) was associated with significantly higher dose response compared with the group of PTCs with point mutations (<jats:italic>BRAF<\/jats:italic>, <jats:italic>RAS<\/jats:italic>; <jats:italic>P<\/jats:italic>\u2009&lt;\u2009.001). In vitro exposure of human thyroid cells to 1 gray of <jats:sup>131<\/jats:sup>I and \u03b3\u2010radiation resulted in the formation of <jats:italic>ETV6\u2010NTRK3<\/jats:italic> rearrangement at a rate of 7.9\u2009\u00d7\u200910<jats:sup>\u22126<\/jats:sup> cells and 3.0\u2009\u00d7\u200910<jats:sup>\u22126<\/jats:sup> cells, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>The authors report the occurrence of <jats:italic>ETV6<\/jats:italic>\u2010<jats:italic>NTRK3<\/jats:italic> rearrangements in thyroid cancer and demonstrate that this rearrangement is significantly more common in tumors associated with exposure to <jats:sup>131<\/jats:sup>I and has a borderline significant dose response. Moreover, <jats:italic>ETV6\u2010NTRK3<\/jats:italic> rearrangement can be directly induced in thyroid cells by ionizing radiation in vitro and, thus, may represent a novel mechanism of radiation\u2010induced carcinogenesis. <jats:bold><jats:italic>Cancer<\/jats:italic> 2014;120:799\u2013807<\/jats:bold>. \u00a9 <jats:italic>2013 American Cancer Society<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.28484","type":"journal-article","created":{"date-parts":[[2013,12,10]],"date-time":"2013-12-10T10:51:35Z","timestamp":1386672695000},"page":"799-807","source":"Crossref","is-referenced-by-count":245,"title":["ETV6\u2010NTRK3 is a common chromosomal rearrangement in radiation\u2010associated thyroid cancer"],"prefix":"10.1002","volume":"120","author":[{"given":"Rebecca J.","family":"Leeman\u2010Neill","sequence":"first","affiliation":[{"name":"Department of Pathology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsey M.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengyuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Physiology and the Cancer Center Medical College of Wisconsin Milwaukee Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina V.","family":"Brenner","sequence":"additional","affiliation":[{"name":"Radiation Epidemiology Branch Division of Cancer Epidemiology and Genetics National Cancer Institute National Institutes of Health Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark P.","family":"Little","sequence":"additional","affiliation":[{"name":"Radiation Epidemiology Branch Division of Cancer Epidemiology and Genetics National Cancer Institute National Institutes of Health Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetiana I.","family":"Bogdanova","sequence":"additional","affiliation":[{"name":"State Institution V. P. Komisarenko Institute of Endocrinology and Metabolism of the Academy of Medical Sciences of Ukraine Kiev Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktoria N.","family":"Evdokimova","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen","family":"Hatch","sequence":"additional","affiliation":[{"name":"Radiation Epidemiology Branch Division of Cancer Epidemiology and Genetics National Cancer Institute National Institutes of Health Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liudmyla Y.","family":"Zurnadzy","sequence":"additional","affiliation":[{"name":"State Institution V. P. Komisarenko Institute of Endocrinology and Metabolism of the Academy of Medical Sciences of Ukraine Kiev Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina N.","family":"Nikiforova","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning J.","family":"Yue","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Cancer Institute of New Jersey University of Medicine and Dentistry of New Jersey\u2010Robert Wood Johnson Medical School New Brunswick New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Cancer Institute of New Jersey University of Medicine and Dentistry of New Jersey\u2010Robert Wood Johnson Medical School New Brunswick New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyohiko","family":"Mabuchi","sequence":"additional","affiliation":[{"name":"Radiation Epidemiology Branch Division of Cancer Epidemiology and Genetics National Cancer Institute National Institutes of Health Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mykola D.","family":"Tronko","sequence":"additional","affiliation":[{"name":"State Institution V. 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