Molecular Landscape in Pediatric and Young Adult Thyroid Cancer: A Brazilian Cohort Study

Thyroid carcinoma in children and adolescents displays distinct molecular features compared with adult disease, with gene fusions playing a prominent oncogenic role. This retrospective multicenter study, representing the largest pediatric thyroid cancer molecular cohort reported from Latin America to date, aimed to characterize the spectrum of molecular alterations in pediatric, adolescent, and young adult patients with differentiated thyroid carcinoma from Northeast Brazil. Seventy-nine tumor samples from patients aged 21 years or younger were analyzed using targeted next-generation sequencing for hotspot point mutations and gene fusions. BRAF^V600E mutations were identified in five cases and excluded from fusion analysis. Among the samples, pathogenic point mutations were detected in 26.6% (21/79), while gene fusions were identified in 13.5% (10/74) of cases. RET rearrangements were observed in 8.6% (03/35) of evaluable tumors, including CCDC6:RET, NCOA4::RET, and TRIM24::RET fusions. Gene fusions overall were significantly more frequent in younger patients, whereas no association was found with tumor size or risk of recurrence. A high proportion of inconclusive results was observed, likely reflecting technical limitations related to the use of formalin-fixed, paraffin-embedded tissue. In conclusion, RET fusions were relatively uncommon in this Brazilian cohort but were enriched in younger patients, underscoring age-related differences in the molecular landscape of pediatric thyroid carcinoma and highlighting the need for larger, standardized multicenter studies.