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.
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 BRAFV600E mutation being the most common event in adult PTC. Although a lower prevalence of BRAFV600E 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 BRAFV600E 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 BRAFV600E 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 BRAFV600E, 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.
Authors: Luiza Sisdelli; Maria Isabel V Cordioli; Fernanda Vaisman; Osmar Monte; Carlos A Longui; Adriano N Cury; Monique O Freitas; Aline Rangel-Pozzo; Sabine Mai; Janete M Cerutti Journal: Biology (Basel) Date: 2021-02-05
Authors: M Herman Chui; Jason C Chang; Yanming Zhang; Ahmet Zehir; Alison M Schram; Jason Konner; Alexander E Drilon; Arnaud Da Cruz Paula; Britta Weigelt; Rachel N Grisham Journal: JCO Precis Oncol Date: 2021-09-16
Authors: Marloes Nies; Rena Vassilopoulou-Sellin; Roland L Bassett; Sireesha Yedururi; Mark E Zafereo; Maria E Cabanillas; Steven I Sherman; Thera P Links; Steven G Waguespack Journal: J Clin Endocrinol Metab Date: 2021-03-25 Impact factor: 5.958
Authors: Sara Jackson; Gyanendra Kumar; Anna B Banizs; Nicole Toney; Jan F Silverman; Christina M Narick; Sydney D Finkelstein Journal: Diagn Cytopathol Date: 2019-11-01 Impact factor: 1.582