A novel loss-of-function deletion in sodium/iodide symporter gene in follicular thyroid adenoma

Area of Science:

• Molecular Biology
• Oncology
• Endocrinology

Background:

• The sodium/iodide symporter (NIS) is crucial for iodide uptake in thyrocytes.
• Down-regulated or mis-targeted NIS expression in thyroid carcinoma correlates with tumor dedifferentiation and reduced radioiodine uptake.
• Understanding NIS gene alterations is vital for diagnosing and treating thyroid cancer.

Purpose of the Study:

• To investigate genetic alterations in the NIS gene in thyroid carcinoma patients.
• To identify novel mutations affecting NIS function and radioiodine uptake capacity.

Main Methods:

• Screening of NIS genes from thyroid tumor tissues using reverse transcription-polymerase chain reaction and nucleotide sequencing.
• Analysis of NIS gene sequences from patient blood.
• Functional assessment of NIS variants using transient transfection and radioiodide uptake assays in HepG2 cells.

Main Results:

• A novel exon 6 deletion in the NIS gene was identified in thyroid tumor tissues.
• The nucleotide sequences flanking the deleted exon 6 were normal in the patient's blood DNA.
• Wild-type NIS-expressing cells showed significantly higher iodide accumulation compared to cells expressing the mutant NIS or mock cells.

Conclusions:

• The identified exon 6 deletion in the NIS gene causes a functional defect in iodide trapping.
• This genetic alteration may contribute to the loss of radioiodine uptake capacity observed in some thyroid carcinomas.
• Further research into NIS gene mutations can improve diagnostic and therapeutic strategies for thyroid cancer.