Coexistence of

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• TERT promoter (TERTp) mutations are significant in papillary thyroid carcinomas (PTCs).
• These mutations correlate with tumor aggressiveness, recurrence, and mortality, suggesting a role in risk stratification.
• Understanding TERTp mutation prevalence and associations in diverse populations is crucial.

Purpose of the Study:

• To determine the prevalence of TERT promoter mutations in a Polish PTC patient cohort.
• To investigate the association of TERTp mutations with histopathological factors, especially when co-occurring with BRAF V600E mutations.

Main Methods:

• Analysis of 189 consecutive PTC specimens with known BRAF mutational status.
• Detection of TERT promoter mutations, including C228T and other alterations.
• Statistical analysis to assess correlations between TERTp mutations, BRAF V600E, and clinicopathological features.

Main Results:

• TERTp mutations were found in 8.5% of PTC cases, with C228T being the most frequent.
• Coexistence of TERTp hotspot mutations and BRAF V600E mutations was significantly associated with male gender, older age, advanced stage, lymph node metastasis, larger tumor size, and capsule infiltration.
• Three novel TERTp alterations were identified alongside a known polymorphism.

Conclusions:

• TERTp mutations are prevalent in Polish PTC patients and frequently co-occur with BRAF V600E mutations.
• The combined presence of TERTp and BRAF V600E mutations is linked to more aggressive clinicopathological features in PTC.
• Further research is needed to confirm TERTp mutations as key drivers of PTC aggressiveness.