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.

Abstract

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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