TERT aberrancies: a screening tool for malignancy in follicular thyroid tumours

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Telomerase reverse transcriptase (TERT) promoter mutations are associated with poor outcomes in thyroid cancer.
• The role of other TERT genetic aberrations in follicular thyroid tumors remains unclear.

Purpose of the Study:

• To investigate the prevalence and clinical significance of TERT gene aberrancies in follicular thyroid tumors.
• To correlate TERT aberrations with tumor type and patient relapse risk.

Main Methods:

• Analysis of TERT expression, promoter mutations, promoter hypermethylation, and gene copy number alterations in follicular carcinomas (FTCs), follicular adenomas (FTAs), and tumors of uncertain malignant potential (FT-UMPs).
• Comparison of molecular findings with clinical parameters, including patient relapse.

Main Results:

• TERT aberrancies (mutation, expression, copy number gain, hypermethylation) were frequent in FTC (59%) and FT-UMP (63%), but rare in FTA.
• FTCs with TERT expression (86%) showed distinct TERT gene aberrations.
• TERT expression, copy number gain, or hypermethylation correlated with an increased risk of relapse in FTCs.

Conclusions:

• TERT expression in follicular thyroid tumors is linked to promoter mutations, copy number gains, and increased methylation.
• Molecular similarities in TERT aberrations between FTC and FT-UMP suggest potential for recurrence in a subset of FT-UMPs.
• TERT aberrancies show promise as biomarkers for assessing the malignant potential of follicular thyroid tumors.