Regulatory SNP of TERT promoter accompanied by C228T and BRAFV600E is an exacerbating factor of papillary thyroid carcinoma

Despite the increased incidence of thyroid cancer due to enhanced precision of ultrasound technology and extensive utilization of puncture aspiration cytology, the mortality rate remains low, raising concerns about overdiagnosis. Papillary thyroid carcinoma (PTC) is the most common type, primarily diagnosed through cell nuclei examination. Recent advancements in identifying genetic mutations and tumor classification have refined diagnostic methods. Point mutations in the telomerase reverse transcriptase promoter (TERTp), specifically ‑124 C >T (C228T) and ‑146 C >T (C250T), and the regulatory single nucleotide polymorphism ‑245 T >C, C allele of rs2853669 (TrSNP) are potential thyroid cancer biomarkers. The present study tested the hypothesis that the coexistence of BRAF mutations in driver genes upstream of the MAPK pathway and late mutations unrelated to signaling, such as point mutations in TERTp, increases tumor virulence. A total of 133 patients with PTC who underwent surgery between January 2014 and November 2021 were included in the study. Blood and tumor tissue samples were collected, and DNA was extracted for genetic mutation analysis using PCR and Sanger sequencing. The TrSNP analysis of blood and surgical tissue samples showed a 97.7% agreement rate. TrSNP was detected in 70 of 133 patients (52.6%) and was significantly associated with tumor size, particularly in tumors >2.0 cm. TERTp point mutations were identified in 29 of 133 patients (21.8%), with C228T strongly associated with tumor size, particularly in tumors >4.0 cm, and extraglandular invasion. BRAFV600E was detected in 82 patients (61.7%) but showed no significant association with clinicopathological parameters. However, the coexistence of BRAFV600E with C228T and TrSNP affected tumor size and progression. The findings indicated that TrSNPs, along with C228T and BRAFV600E, may serve as potential molecular markers to predict PTC growth or exacerbation. Notably, coexistence of C228T and TrSNP is a preoperative indicator of disease progression.