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Molecular pathogenesis of pediatric thyroid carcinoma

There has been little understanding of the molecular pathogenesis of pediatric thyroid cancers. Most of them are histologically classified as papillary thyroid carcinoma (PTC). Ionizing radiation is the most important environmental factor to induce PTC, especially in children. Particularly, radiatio...

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Autores principales: Mitsutake, Norisato, Saenko, Vladimir
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114219/
https://www.ncbi.nlm.nih.gov/pubmed/33978172
http://dx.doi.org/10.1093/jrr/rraa096
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author Mitsutake, Norisato
Saenko, Vladimir
author_facet Mitsutake, Norisato
Saenko, Vladimir
author_sort Mitsutake, Norisato
collection PubMed
description There has been little understanding of the molecular pathogenesis of pediatric thyroid cancers. Most of them are histologically classified as papillary thyroid carcinoma (PTC). Ionizing radiation is the most important environmental factor to induce PTC, especially in children. Particularly, radiation-related pediatric PTCs after the Chernobyl accident provided invaluable information. In addition, the recent accumulation of sporadic pediatric PTC cases, partly due to advances in diagnostic imaging, has also provided insight into their general pathogenesis. In PTC development, basically two types of genetic alterations, fusion oncogenes, mainly RET/PTC, and a point mutation, mainly BRAF(V600E), are thought to play a key role as driver oncogenes. Their frequencies vary depending on patient age. The younger the age, the more prevalent the fusion oncogenes are. Higher incidence of fusion oncogenes was also observed in cases exposed to radiation. In short, fusion oncogenes are associated with both age and radiation and are not evidence of radiation exposure. The type of driver oncogene is shifted toward BRAF(V600E) during adolescence in sporadic PTCs. However, until about this age, fusion oncogenes seem to still confer dominant growth advantages, which may lead to the higher discovery rate of the fusion oncogenes. It has been postulated that RET/PTC in radiation-induced PTC is generated by ionizing radiation; however, there is an interesting hypothesis that thyroid follicular cell clones with pre-existing RET/PTC were already present, and radiation may play a role as a promoter/progressor but not initiator. Telomerase reverse transcriptase gene (TERT) promoter mutations, which are the strongest marker of tumor aggressiveness in adult PTC cases, have not been detected in pediatric cases; however, TERT expression without the mutations may play a role in tumor aggressiveness. In this paper, the recent information regarding molecular findings in sporadic and radiation-associated pediatric PTCs is summarized.
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spelling pubmed-81142192021-05-17 Molecular pathogenesis of pediatric thyroid carcinoma Mitsutake, Norisato Saenko, Vladimir J Radiat Res Fundamental Radiation Science There has been little understanding of the molecular pathogenesis of pediatric thyroid cancers. Most of them are histologically classified as papillary thyroid carcinoma (PTC). Ionizing radiation is the most important environmental factor to induce PTC, especially in children. Particularly, radiation-related pediatric PTCs after the Chernobyl accident provided invaluable information. In addition, the recent accumulation of sporadic pediatric PTC cases, partly due to advances in diagnostic imaging, has also provided insight into their general pathogenesis. In PTC development, basically two types of genetic alterations, fusion oncogenes, mainly RET/PTC, and a point mutation, mainly BRAF(V600E), are thought to play a key role as driver oncogenes. Their frequencies vary depending on patient age. The younger the age, the more prevalent the fusion oncogenes are. Higher incidence of fusion oncogenes was also observed in cases exposed to radiation. In short, fusion oncogenes are associated with both age and radiation and are not evidence of radiation exposure. The type of driver oncogene is shifted toward BRAF(V600E) during adolescence in sporadic PTCs. However, until about this age, fusion oncogenes seem to still confer dominant growth advantages, which may lead to the higher discovery rate of the fusion oncogenes. It has been postulated that RET/PTC in radiation-induced PTC is generated by ionizing radiation; however, there is an interesting hypothesis that thyroid follicular cell clones with pre-existing RET/PTC were already present, and radiation may play a role as a promoter/progressor but not initiator. Telomerase reverse transcriptase gene (TERT) promoter mutations, which are the strongest marker of tumor aggressiveness in adult PTC cases, have not been detected in pediatric cases; however, TERT expression without the mutations may play a role in tumor aggressiveness. In this paper, the recent information regarding molecular findings in sporadic and radiation-associated pediatric PTCs is summarized. Oxford University Press 2021-05-05 /pmc/articles/PMC8114219/ /pubmed/33978172 http://dx.doi.org/10.1093/jrr/rraa096 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Fundamental Radiation Science
Mitsutake, Norisato
Saenko, Vladimir
Molecular pathogenesis of pediatric thyroid carcinoma
title Molecular pathogenesis of pediatric thyroid carcinoma
title_full Molecular pathogenesis of pediatric thyroid carcinoma
title_fullStr Molecular pathogenesis of pediatric thyroid carcinoma
title_full_unstemmed Molecular pathogenesis of pediatric thyroid carcinoma
title_short Molecular pathogenesis of pediatric thyroid carcinoma
title_sort molecular pathogenesis of pediatric thyroid carcinoma
topic Fundamental Radiation Science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114219/
https://www.ncbi.nlm.nih.gov/pubmed/33978172
http://dx.doi.org/10.1093/jrr/rraa096
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