Uncommon TERT Promoter Mutations in Pediatric Thyroid Cancer

The aim of this study was to determine the rate and significance of TERT promoter mutations that have been recently described in adult thyroid cancer (TC) but not yet in the uncommonly occurring pediatric TC. Furthermore, the role of the BRAF(V600E) mutation in the clinical outcome of pediatric TC is unknown.

The study included 55 pediatric (median age 16 years, range 9-18 years; 46 females) and 210 adult TC patients (median age 40 years, range 20-75 years; 155 females) seen during the same time period. DNA was isolated from TC tissues and subjected to direct sequencing. Genetic-clinicopathological correlations were analyzed.

Only one case of pediatric TC was found to harbor the C228T TERT promoter mutation (1.8%). The C250T mutation was not detected in any of the 55 pediatric TC. In contrast, there was a significantly higher rate of TERT promoter mutations in the adult patients (15.7%, 33/210) compared with the pediatric patients (p = 0.003). In addition, persistent/recurrent TC was seen in 8/12 (66.7%) pediatric patients harboring the BRAF(V600E) mutation versus 14/41 (34.1%) patients harboring the wild type BRAF (p = 0.05), and when only conventional papillary TC was examined, in 7/9 (77.8%) cases harboring BRAF(V600E) mutation versus 11/33 (33.3%) cases harboring wild type BRAF (p = 0.025).

This is the first study on TERT promoter mutations in pediatric TC, which revealed an exceedingly low prevalence, suggesting a limited role of these mutations in pediatric TC. This study also for the first time demonstrates an association of the BRAF(V600E) mutation with TC recurrence in pediatric patients.