Explore the groundbreaking insights into the genetic landscape that influences radioiodine treatment effectiveness in metastatic thyroid cancer, paving the way for personalized nuclear medicine strategies.
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Characterizing genetic alterations related to radioiodine avidity in metastatic thyroid cancer.
Mu et al., J Clin Endocrinol Metab 2023
DOI: 10.1210/clinem/dgad697
Summary of Genetic Features in Radioactive Iodine Uptake Patterns of Distant Metastatic Differentiated Thyroid Cancer (DM-DTC)
Background: Identifying genetic markers for radioactive iodine (RAI) uptake patterns in DM-DTC can help in early detection of RAI-refractory DTC.
Methods: A retrospective study of 214 DM-DTC patients was conducted. RAI uptake patterns were categorized as initially RAI-refractory (I-RAIR) or initially RAI-avid (I-RAIA), with I-RAIA further divided into continually RAIA (C-RAIA), partly RAIR (P-RAIR), and gradually RAIR (G-RAIR). Patients were grouped by driver gene status: BRAFV600E-mutated, RAS-mutated, fusions, and others.
Results: I-RAIR patterns were associated with BRAF, TERT promoter, and TP53 mutations. RET fusions and RAS mutations were more common in I-RAIA patterns. Late-hit mutations (TERT, TP53, or PIK3CA) were found in 50.0% of I-RAIR versus 26.9% of I-RAIA (P = 0.001). RAS mutations in I-RAIR often co-occurred with TERT promoter mutations. Isolated RET fusions were present in 10% of I-RAIR cases. BRAFV600E-mutated tumors had a higher rate of I-RAIR (63.5%) compared to RAS-mutated (12.5%, P < 0.001) and fusions-positive (20.7%, P < 0.001) tumors. In I-RAIA subgroups, BRAFV600E-mutated tumors had a lower prevalence of C-RAIA pattern compared to those with RAS mutations or fusions.
Significance: The study highlights the correlation between genetic mutations and RAI uptake patterns in DM-DTC. BRAF and/or TERT promoter mutations are predominant in I-RAIR patterns, with RAS mutations often linked to additional late-hit mutations. These findings could contribute to the early identification and management of RAI-refractory DTC.