Analysis of genetic alterations associated with radioiodine avidity in metastatic thyroid cancer

Below is a summary of “Characterization of Genetic Alterations Associated with Radioiodine Avidity in Metastatic Thyroid Cancer,” published in the May 2024 issue of Endocrinology by Mu, et al.

Patients with differentiated thyroid cancer (DTC) often face challenges in timely recognition of refractory radioactive iodine (RAI) disease, especially in cases with distant metastases (DM). Understanding the genetic features associated with RAI uptake patterns may help in the early identification of RAI-refractory DTC. For one study, researchers sought to uncover the molecular characteristics underlying different patterns of RAI uptake in patients with DTC and distant metastases.

A retrospective analysis included 214 patients with DM-DTC. RAI uptake patterns were classified as initially refractory RAI (I-RAIR) or initially avid RAI (I-RAIA), with further subcategorization of I-RAIA into persistently avid RAI (C-RAIA), partially refractory RAI (P- RAIR), and gradually refractory RAI (G-RAIR). Molecular subtypesBRAFV600Emutation, RAS mutation, fusions, and others were defined based on primary driver gene status.

In the analysis, BRAF, THIRD promoter, and TP53 mutations were most frequently identified in the initial radioactive iodine refractory (I-RAIR) model, while RoT fusions and RAS mutations were more prevalent in the initial radioactive iodine model (I-RAIA). Emergence of late hit mutations involving TERT, TP53OR PIK3CA was significantly higher in I-RAIR compared to I-RAIA (50.0% vs. 26.9%, P = .001), especially in cases with RAS mutations in the I-RAIR group, which were consistently accompanied by TERT promoter mutations. Isolated RoT fusions accounted for 10% of the cases in the I-RAIR model. When different sets of driver genes are compared, BRAFV600EMutated tumors showed a higher incidence of the I-RAIR pattern (64.4%) than with RAS mutation (4.5%) P < .001) and fusion-positive (20.7%, P < .001) tumors. Within the I-RAIA subgroups, BRAFV600EMutated tumors showed a lower prevalence of continuous radioactive iodine pattern (C-RAIA) compared to tumors with RAS mutations or fusions.

Patients with the I-RAIR pattern mainly displayed BRAF and/or TERT promoter mutations, often accompanied by RAS mutations, whereas fusions usually occurred alone. The findings provided insight into the molecular landscape associated with patterns of RAI uptake in DTC with distant metastases.


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