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Context Pediatric differentiated thyroid cancer (DTC) differs from adult DTC in its underlying genetics and clinicopathological features. In this report, we studied these aspects in 48 cases of pediatric DTC. Patients and Methods We used the comprehensive Oncomine Childhood Cancer Gene panel on Ion Torrent next-generation sequencing platform. We included 48 patients (37 girls and 11 boys) with pediatric DTC (median age 17 years; range, 5-18 years) and studied the association between these genetic alterations and the clinicopathological features and outcome. Results Of 48 tumors, 33 (69%) had somatic genetic alterations that were mutually exclusive except in one tumor. BRAFV600E and RET-PTC1 were the most common, occurring in 9 different tumors (19%) each. RET-PTC3 and ETV6-NTRK3 were the next most common, with each occurring in 4 different tumors (8%). Other genetic alterations including EML4-NTRK1, EML4-ALK, NRAS, KRAS, PTEN, and CREBBP occurred once each. There were no differences between those who had mutations and those without mutations with respect to age, sex, tumor multifocality, extrathyroidal extension, vascular invasion, lymph node or distant metastasis, and American Thyroid Association response to therapy status at the last follow-up visits. Similarly, none of these factors was different between those with fusion genes vs single-point mutations vs no mutations. Conclusions In pediatric DTC, fusion genes are more common than single-point mutations. The most common genetic alterations are RET-PTC1, BRAFV600E, RET-PTC3, and ETV6-NTRK3. Other alterations occur rarely. Genetic alterations do not correlate with the clinicopathological features or the outcome.

Genetic Alterations in Pediatric Thyroid Cancer Using a Comprehensive Childhood Cancer Gene Panel