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Published on: August 23, 2019
BRAF mutations in papillary thyroid carcinomas inhibit genes involved in iodine metabolism
C Durante1, E Puxeddu, E Ferretti
1Department of Clinical Sciences, University of Rome La Sapienza, 00161 Rome, Italy.
Context:
BRAF mutations are common in papillary thyroid carcinomas (PTCs). By affecting the expression of genes critically related to the development and differentiation of thyroid cancer, they may influence the prognosis of these tumors.
Objective:
Our objective was to characterize the expression of thyroid-specific genes associated with BRAF mutation in PTCs. DESIGN/SETTING AND PATIENTS: We examined the expression of key markers of thyrocyte differentiation in 56 PTCs with BRAF mutations (BRAF-mut) and 37 with wild-type BRAF (BRAF-wt). Eight samples of normal thyroid tissue were analyzed as controls. Quantitative PCR was used to measure mRNA levels for the sodium/iodide symporter (NIS), apical iodide transporter (AIT-B), thyroglobulin (Tg), thyroperoxidase (TPO), TSH receptor (TSH-R), the transcription factor PAX8, and glucose transporter type 1 (Glut1). NIS protein expression and localization was also analyzed by immunohistochemistry.
Results:
mRNA levels for all thyroid-specific genes were reduced in all PTCs vs. normal thyroid tissues. NIS, AIT-B, Tg, and TPO expression was significantly lower in BRAF-mut tumors than in the BRAF-wt group. Glut-1 transcript levels were increased in all PTCs, and additional increases were noted in BRAF-mut tumors. In both tumor subsets, the NIS protein that was expressed was abnormally retained in the cytoplasm.
Conclusion:
BRAF V600E mutation in PTCs is associated with reduced expression of key genes involved in iodine metabolism. This effect may alter the effectiveness of diagnostic and/or therapeutic use of radioiodine in BRAF-mut PTCs.
Insights
BRAF mutations in papillary thyroid cancer (PTC) reduce the expression of genes crucial for iodine metabolism, potentially impacting radioiodine therapy effectiveness. This study analyzed key thyroid-specific gene expression in PTCs with and without BRAF mutations.
Area of Science:
- Endocrinology
- Oncology
- Molecular Biology
Background:
- BRAF mutations are prevalent in papillary thyroid carcinomas (PTCs).
- These mutations can influence the expression of genes critical for thyroid cancer development and prognosis.
Purpose of the Study:
- To characterize the expression of thyroid-specific genes in PTCs with BRAF mutations.
- To compare gene expression profiles between PTCs with BRAF mutations (BRAF-mut) and wild-type BRAF (BRAF-wt).
Main Methods:
- Quantitative PCR was used to measure mRNA levels of sodium/iodide symporter (NIS), apical iodide transporter (AIT-B), thyroglobulin (Tg), thyroperoxidase (TPO), TSH receptor (TSH-R), PAX8, and glucose transporter type 1 (Glut1).
- Immunohistochemistry was employed to analyze NIS protein expression and localization.
- 56 BRAF-mut PTCs, 37 BRAF-wt PTCs, and 8 normal thyroid tissue samples were analyzed.
Main Results:
- All thyroid-specific genes showed reduced mRNA levels in PTCs compared to normal thyroid tissue.
- NIS, AIT-B, Tg, and TPO expression were significantly lower in BRAF-mut PTCs than in BRAF-wt PTCs.
- Glut-1 transcript levels were elevated in all PTCs, with further increases in BRAF-mut tumors. NIS protein was abnormally retained in the cytoplasm in both tumor groups.
Conclusions:
- BRAF V600E mutation in PTC is linked to decreased expression of key genes involved in iodine metabolism.
- This downregulation may affect the efficacy of diagnostic and therapeutic radioiodine applications in BRAF-mut PTCs.
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