TERT promoter mutations in thyroid cancer

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• The discovery of Telomerase reverse transcriptase (TERT) promoter mutations (C228T and C250T) in 2013 significantly advanced thyroid cancer research.
• TERT promoter mutations contribute to oncogenesis by creating binding sites for E-twenty-six transcriptional factors.

Purpose of the Study:

• To provide a comprehensive review of the role and clinical utility of TERT promoter mutations in thyroid cancer.
• To discuss the association of TERT promoter mutations with tumor aggressiveness, recurrence, and patient mortality.

Main Methods:

• Review of existing literature on TERT promoter mutations in thyroid cancer.
• Analysis of mutation prevalence across different thyroid tumor types.
• Examination of the synergistic effects with BRAF V600E mutations.

Main Results:

• TERT promoter mutations are prevalent in aggressive thyroid cancers (43.2% in poorly differentiated, 40.1% in anaplastic).
• TERT C228T is more common than TERT C250T.
• Coexistence of TERT promoter and BRAF V600E mutations synergistically increases PTC aggressiveness, recurrence, and mortality.

Conclusions:

• TERT promoter mutations are significant oncogenes in thyroid cancer.
• These mutations are promising diagnostic and prognostic markers, especially when combined with BRAF V600E or RAS mutations.
• Further research is needed to define clinical utility, elucidate mechanisms, and explore therapeutic targeting.