AUTHOR=McKelvey Brittany A. , Umbricht Christopher B. , Zeiger Martha A. 

TITLE=Telomerase Reverse Transcriptase (TERT) Regulation in Thyroid Cancer: A Review

JOURNAL=Frontiers in Endocrinology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2020.00485

DOI=10.3389/fendo.2020.00485

ISSN=1664-2392

ABSTRACT=<p><italic>Telomerase reverse transcriptase (TERT)</italic> is the catalytic subunit of the enzyme telomerase and is essential for telomerase activity. Upregulation of <italic>TERT</italic> expression and resulting telomerase activity occurs in the large majority of malignancies, including thyroid cancer. This upregulation results in continued cellular proliferation and avoidance of cellular senescence and cell death. In this review we will briefly introduce <italic>TERT</italic> and telomerase activity as it pertains to thyroid cancer and, highlight the effects of <italic>TERT</italic> on cancer cells. We will also explore in detail the different <italic>TERT</italic> regulatory strategies and how <italic>TERT</italic> is reactivated in thyroid cancer cells, specifically. These regulatory mechanisms include both activating single base pair <italic>TERT</italic> promoter mutations and epigenetic changes at the promoter, including changes in CpG methylation and histone modifications that affect chromatin structure. Further, regulation includes the allele-specific regulation of the <italic>TERT</italic> promoter in thyroid cancer cells harboring the <italic>TERT</italic> promoter mutation. These entail allele-specific transcriptional activator binding, DNA methylation, histone modifications, and mono-allelic expression of <italic>TERT</italic>. Lastly, <italic>TERT</italic> copy number alterations and alternative splicing are also implicated. Both amplifications of the <italic>TERT</italic> locus and increased full-length transcripts and decreased inactive and dominant negative isoforms result in active telomerase. Finally, the clinical significance of <italic>TERT</italic> in thyroid cancer is also reviewed.</p>