Genomic Differences in Thyroid Cancers From Primary Sites Versus Distant Metastases in Individual Patients: A Clinical Perspective and Preliminary Report

Background: Distant metastasis is a leading cause of thyroid cancer (TC)-related deaths. Genetic profiling is typically limited to one sample per patient due to cost and sampling-risk concerns. Differences between samples from thyroid and distant metastasis within individual patients are unclear. Methods: Patients with TC and distant metastasis were recruited for genetic analysis. Results: Using a TC-specific NGS panel, 66 specimens from 29 patients were analyzed, identifying 16 mutations and 4 fusions, including two novel fusions (FGFR2–SHTN1 and RFTN1–BRAF). Genetic alterations differed between primary and metastatic sites in nine patients (31%), predominantly in additional oncogenic alterations (89%). More genetic alterations were found at the primary site in three patients and metastatic sites in four. Distinct mutations were found in two patients. A longer time interval between specimen acquisitions was significantly associated with genetic discrepancies (p = 0.032). Conclusion: Patterns of genetic discrepancies between primary and metastatic TC vary, offering valuable insights for clinical practice.