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Author Spotlight: Advancing the Detection of Low-Frequency Mutations in Cancer Tissues
Published on: August 23, 2024
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IGF2 is a potential factor in RAI-refractory differentiated thyroid cancer.
Thomas Crezee1,2, Marika H Tesselaar1,2, Martin Jaeger2,3
1Department of Pathology, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands.
Oncology Letters
|June 21, 2021
Summary
Radioactive iodide (RAI) therapy resistance in differentiated thyroid cancer (DTC) may be linked to specific genetic mutations and increased insulin-like growth factor 2 (IGF2) expression, offering potential biomarkers for treatment response.
Area of Science:
- Endocrinology
- Oncology
- Molecular Biology
Background:
- Differentiated thyroid cancer (DTC) is common, but 30-40% of metastatic cases resist radioactive iodide (RAI) treatment due to tumor dedifferentiation.
- Molecular mechanisms driving RAI resistance and dedifferentiation in DTC are not fully understood, and predictive biomarkers are lacking.
Purpose of the Study:
- To identify molecular biomarkers in primary tumors associated with resistance to radioactive iodide (RAI) treatment in differentiated thyroid cancer (DTC).
Main Methods:
- Retrospective analysis of RAI-sensitive and RAI-refractory DTC patient cohorts.
- Intratumoral mutation profiling, gene fusion analysis, TERT promoter mutation analysis, and RNA sequencing.
- ELISA for plasma insulin-like growth factor 2 (IGF2) concentrations.
Main Results:
- RAI-refractory DTC exhibited increased mutational load, including mutations in AKT1, PTEN, TP53, and TERT promoter.
- Significantly higher IGF2 expression (up to 100-fold) was observed in RAI-refractory DTC compared to RAI-sensitive cases.
- Lower post-treatment IGF2 plasma concentrations were detected in DTC patients compared to baseline.
Conclusions:
- Increased mutational load and elevated IGF2 expression are associated with RAI refractoriness in differentiated thyroid cancer.
- IGF2 may play a role in the development of RAI refractoriness, suggesting its potential as a predictive biomarker.
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