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AGK‐BRAF is associated with distant metastasis and younger age in pediatric papillary thyroid carcinoma

2019; Wiley; Volume: 66; Issue: 7 Linguagem: Inglês

10.1002/pbc.27707

1545-5017

Luiza Sisdelli, Maria Isabel Cunha Vieira Cordioli, Fernanda Vaisman, Laís Moraes, Gabriel Avelar Colozza‐Gama, Paulo Alonso Garcia Alves, Mário Lúcio Cordeiro Araujo, Maria Teresa Seixas Alves, Osmar Monte, Carlos Alberto Longui, Adriano Namo Cury, Gianna Carvalheira, Janete M. Cerutti,

S100 Proteins and Annexins

Abstract Background The incidence of thyroid carcinoma has increased in most populations, including pediatric patients. The increase is almost exclusively due to an increase in the incidence of papillary thyroid carcinoma (PTC). Genetic alterations leading to mitogen‐activated protein kinase (MAPK) pathway activation are highly prevalent in PTC, with BRAF V600E mutation being the most common event in adult PTC. Although a lower prevalence of BRAF V600E had been reported among pediatric patients, a higher prevalence of BRAF fusion has been identified in both radiation‐exposed and sporadic pediatric PTC. However, little is known about the prognostic implications of BRAF fusions in pediatric PTC. Procedure In this study, we investigated the prevalence of BRAF alterations ( AGK‐BRAF fusion and BRAF V600E mutation) in a large set of predominantly sporadic pediatric PTC cases and correlate with clinicopathological features. Somatic AGK‐BRAF fusion was investigated by RT‐PCR and confirmed by FISH break‐apart. The BRAF V600E mutation was screened using Sanger sequencing. Results AGK‐BRAF fusion, found in 19% of pediatric PTC patients, was associated with distant metastasis and younger age. Conversely, the BRAF V600E, found in 15% of pediatric PTC patients, was correlated with older age and larger tumor size. Conclusion Collectively, our results advance knowledge concerning genetic bases of pediatric thyroid carcinoma, with potential implications for diagnosis, prognosis, and therapeutic approaches.