High Incidence of Mutations in Follicular Thyroid Cancer: Potential Therapeutic Target in Patients with Advanced Disease Stage

Background: Conventional treatments for follicular thyroid cancer (FTC) can be ineffective, leading to poor prognosis. The aim of this study was to identify mutations associated with FTC that would serve as novel molecular markers of the disease and its outcome and could potentially identify new therapeutic targets.

Methods: mutations were first detected in a 29-year-old White female diagnosed with metastasized, treatment-refractory FTC. Analyses of mutational status through next-generation sequencing of formalin-fixed, paraffin-embedded FTC specimens were subsequently performed in 35 randomly selected patients diagnosed with FTC.

Results: mutations were found in 69% of patients. mutation-positive patients were significantly older than those that were mutation-negative [median age at diagnosis 54 (36-82) 45 (27-58) ( = 0.023)]. Patients over 60 years were 23 times more likely to be mutation-positive ( = 0.006). However, the number of mutations did not correlate with age (-Pearson: -0.244, -value: 0.25). A total of 26 mutations were identified in the gene with 2-16 mutations in each mutation-positive patient (mean: 5.6 mutations/patient). Tyrosine kinase domain (TKD) mutations in the gene were detected in 58% of mutation-positive patients. All mutation-positive patients with a disease stage of pT2N1 or worse harbored at least one mutation in the TKD of .

Conclusions: There is a wide spectrum and high frequency of mutations in FTC. The precise role of mutations in the genesis of FTC, as well as its potential role as a therapeutic target, requires further investigation.