Somatic Mutational Landscape in Follicular Thyroid Cancer: Insights from AACR GENIE Data

<b>Objective(s):</b> To delineate the somatic mutational landscape of follicular thyroid carcinoma (FTC) from a large, real-world cohort to identify molecular subtypes and actionable targets for personalized therapeutic interventions. <b>Methods:</b> Genomic and clinical data for 168 FTC samples were retrieved from the AACR Project GENIE^® registry via cBioPortal. This study assessed mutation frequencies, copy number alterations, and subgroup differences (primary vs. metastatic; adult vs. pediatric) using statistical tests. <b>Results:</b> NRAS was the most common mutation (33.9%), followed by TERT (22.6%), DICER1 (15.5%), HRAS (11.9%), and PTEN (10.7%). DICER1 mutations were significantly enriched in pediatric cases (44.4% vs. 4.6% in adults, <i>p</i> < 0.001), while TERT mutations were exclusive to adults (42%). NRAS mutations were more frequent in metastatic tumors (42.4%) than primary tumors (29.2%). <b>Conclusions:</b> FTC tumorigenesis is driven by distinct molecular pathways, with significant heterogeneity between pediatric and adult patients as well as primary and metastatic disease. These findings underscore the necessity of molecular profiling for patient stratification and provide a strong rationale for developing personalized treatment strategies to improve clinical outcomes.