Fusion Oncogenes Are the Main Genetic Events Found in Sporadic Papillary Thyroid Carcinomas from Children

Fusion Oncogenes Are the Main Genetic Events Found in Sporadic Papillary Thyroid Carcinomas from Children

Author Vieira Cordioli Autor UNIFESP Google Scholar
Moraes, Lais Autor UNIFESP Google Scholar
Bastos, Andre U. Autor UNIFESP Google Scholar
Besson, Paloma Autor UNIFESP Google Scholar
de Seixas Alves, Maria Teresa Autor UNIFESP Google Scholar
Delcelo, Rosana Autor UNIFESP Google Scholar
Monte, Osmar Google Scholar
Longui, Carlos Google Scholar
Cury, Adriano Namo Google Scholar
Cerutti, Janete M. Autor UNIFESP Google Scholar
Abstract Background: Previous studies reported significant differences in the clinical presentation and outcomes of papillary thyroid carcinoma (PTC) in pediatric patients compared with adults. Previous studies have suggested that the clinicopathological differences observed between pediatric and adult PTCs may be due the existence of distinct genetic alterations. However, the knowledge of genetic events in pediatric PTCs is based primarily on studies in radiation-exposed PTCs or in the few studies that enrolled predominantly adolescent patients. The aim of this study was to characterize the known oncogenic alterations of the MAPK pathway found in adult and radiation-exposed PTCs in a cohort of predominantly sporadic pediatric PTC patients. Methods: Thirty-five pediatric PTCs were screened for the most prevalent fusions (RET/PTC1, RET/PTC2, RET/PTC3, ETV6-NTRK3, and AGK-BRAF) and point mutations (BRAF(V600E) and NRAS(Q61)) described in sporadic pediatric PTCs. The mutational status was correlated with clinicopathological data. Results: Mutations were found in 20 out of 35 (57%) PTC cases. Fusion oncogenes were the main genetic alterations found. RET/PTC1-3 rearrangements were found in 13 (37%), ETV6-NTRK3 in 3 (9%), AGK-BRAF in 4 (11%), and BRAF(V600E) in 3 (9%). No mutation was found in NRAS(Q61). BRAF(V600E) was associated with older age and larger tumor size (p < 0.05), and RET/PTC3 was associated with a larger tumor size and multifocality (p < 0.05). Conclusions: The genetic signature in this cohort was remarkably different than that observed in adults. Although observed at a lower prevalence, the spectrum of mutations was quite similar to that described in radiation-exposed pediatric PTCs. As mutations were unidentifiable in over 40% of the PTC cases, more comprehensive studies conducted in these patients will help to decipher the genetic landscape of sporadic pediatric PTCs.
Keywords pediatric thyroid carcinomas
BRAF
RET/PTC
ETV6-NTRK3
AGK-BRAF
xmlui.dri2xhtml.METS-1.0.item-coverage New Rochelle
Language English
Sponsor Sao Paulo State Research Foundation
Brazilian Research Council
Sao Paulo State Research Foundation
Grant number FAPESP: 2013/03867-5
FAPESP: 2015/60330-8
CNPq: 470441/2013-5
Date 2017
Published in Thyroid. New Rochelle, v. 27, n. 2, p. 182-188, 2017.
ISSN 1050-7256 (Sherpa/Romeo, impact factor)
Publisher Mary Ann Liebert, Inc
Extent 182-188
Origin http://dx.doi.org/10.1089/thy.2016.0387
Access rights Closed access
Type Article
Web of Science ID WOS:000394051600008
URI https://repositorio.unifesp.br/handle/11600/55182

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