Highly prevalent TERT promoter mutations in aggressive thyroid cancers.

Area of Science:

• Oncology
• Genetics
• Molecular Biology

Background:

• Telomerase reverse transcriptase (TERT) promoter mutations are implicated in various human cancers.
• These mutations have not been previously reported in thyroid cancers.
• Understanding the role of TERT mutations in thyroid tumorigenesis is crucial.

Purpose of the Study:

• To investigate the presence and prevalence of TERT promoter mutations (C228T and C250T) in a diverse cohort of thyroid tumors.
• To determine the association of TERT promoter mutations with different thyroid cancer subtypes and BRAF V600E mutation status.

Main Methods:

• Genomic sequencing of primary thyroid tumor samples.
• Analysis of mutations in benign thyroid tumors, papillary thyroid cancers (PTC), follicular thyroid cancers (FTC), poorly differentiated thyroid cancers (PDTC), anaplastic thyroid cancers (ATC), and thyroid cancer cell lines.
• Statistical analysis to assess associations between TERT mutations, cancer subtypes, and BRAF mutations.

Main Results:

• TERT promoter mutations (C228T and C250T) were detected in various thyroid cancer types, with higher prevalence in aggressive subtypes: PDTC (37.5%), ATC (42.6%), and thyroid cancer cell lines (66.7% and 91.7%).
• C228T mutation was found in PTC (11.7%), FTC (11.4%), and specifically in tall-cell PTC (30.8%).
• TERT mutations were mutually exclusive and significantly associated with BRAF V600E mutation in PTC (P=0.0094).

Conclusions:

• This study provides the first evidence of TERT promoter mutations in thyroid cancers.
• TERT mutations are prevalent in aggressive thyroid cancer subtypes and are linked to BRAF V600E mutations in PTC.
• These findings reveal a novel genetic landscape for thyroid cancers, particularly aggressive forms.