The role of TERT promoter mutations in postoperative and preoperative diagnosis and prognosis in thyroid cancer.

BACKGROUND: Telomerase reverse transcriptase (TERT) promoter mutations have been described in different pathological types of thyroid cancers (TC). After many types of research focusing on the mutations rate in malignant tumors, the main role of TERT promoter mutations has been changed to the preoperative diagnosis and prognosis of TC, according to their high prevalence in aggressive TC.

METHODS: We searched Pubmed, Web of Science, Scopus, and VHL and reviewed the most common 2 mutations C288T and C250T in different types of TC, the association between them and some specific clinicopathological features, and their significance in preoperative diagnosis and prognosis of TC. we chose 38 studies into our qualitative research. We also chose 22 studies to do a meta-analysis on this subject.

RESULTS: The overall rate of these mutations in different types of TC was 10.0%, with 86.1% C228T mutation, 12% C250T mutation, and 2.1% other type mutations. The rate increases significantly as the TC become more aggressive, and reaches 56.8% in anaplastic thyroid cancer (ATC). Statistically meaningful association is found between TERT promoter mutations and older age, larger tumor size, extrathyroidal extension, lymph node metastasis, distance metastasis, advanced TNM stage, recurrence, and BRAF V600E mutation. Some studies concentrating on DNA sequencing based on fine needle aspiration biopsy (FNAB) also proved their significance in preoperative stage, with 7% to 16.5% sensitivity.

CONCLUSIONS: TERT promoter mutations were likely to occur in BRAF V600E positive TC. Patients with these 2 combined mutations were more likely to have a poor prognosis and outcome. TERT promoter mutations is an essential part of the ThySeq gene panel. The mechanism of how they influence the appearance and development of TC has not been expounded. The next study direction may be the mechanism exploration and the further study to prove their significance in preoperative diagnosis.