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

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dc.citation.issue2
dc.citation.volume27
dc.contributor.authorVieira Cordioli [UNIFESP], Maria Isabel C. [UNIFESP]
dc.contributor.authorMoraes, Lais [UNIFESP]
dc.contributor.authorBastos, Andre U. [UNIFESP]
dc.contributor.authorBesson, Paloma [UNIFESP]
dc.contributor.authorde Seixas Alves, Maria Teresa [UNIFESP]
dc.contributor.authorDelcelo, Rosana [UNIFESP]
dc.contributor.authorMonte, Osmar
dc.contributor.authorLongui, Carlos
dc.contributor.authorCury, Adriano Namo
dc.contributor.authorCerutti, Janete M. [UNIFESP]
dc.coverageNew Rochelle
dc.date.accessioned2020-07-17T14:03:08Z
dc.date.available2020-07-17T14:03:08Z
dc.date.issued2017
dc.description.abstractBackground: 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.en
dc.description.affiliationUniv Fed Sao Paulo, Genet Bases Thyroid Tumors Lab, Div Genet, Dept Morphol & Genet, Sao Paulo, SP, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Div Endocrinol, Dept Med, Sao Paulo, SP, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Pathol, Escola Paulista Med, Sao Paulo, SP, Brazil
dc.description.affiliationIrmandade Santa Casa Misericordia, Fac Ciencias Med, Dept Med, Div Pediat, Sao Paulo, SP, Brazil
dc.description.affiliationIrmandade Santa Casa Misericordia, Fac Ciencias Med, Dept Med, Div Endocrinol, Sao Paulo, SP, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Div Endocrinol, Dept Med, Sao Paulo, SP, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Pathol, Escola Paulista Med, Sao Paulo, SP, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipSao Paulo State Research Foundation
dc.description.sponsorshipBrazilian Research Council
dc.description.sponsorshipSao Paulo State Research Foundation
dc.description.sponsorshipIDFAPESP: 2013/03867-5
dc.description.sponsorshipIDFAPESP: 2015/60330-8
dc.description.sponsorshipIDCNPq: 470441/2013-5
dc.format.extent182-188
dc.identifierhttp://dx.doi.org/10.1089/thy.2016.0387
dc.identifier.citationThyroid. New Rochelle, v. 27, n. 2, p. 182-188, 2017.
dc.identifier.doi10.1089/thy.2016.0387
dc.identifier.issn1050-7256
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/55182
dc.identifier.wosWOS:000394051600008
dc.language.isoeng
dc.publisherMary Ann Liebert, Inc
dc.relation.ispartofThyroid
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectpediatric thyroid carcinomasen
dc.subjectBRAFen
dc.subjectRET/PTCen
dc.subjectETV6-NTRK3en
dc.subjectAGK-BRAFen
dc.titleFusion Oncogenes Are the Main Genetic Events Found in Sporadic Papillary Thyroid Carcinomas from Childrenen
dc.typeinfo:eu-repo/semantics/article
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