Telomerase reverse transcriptase (TERT) is the catalytic subunit of telomerase. Telomerase, an RNA-dependent DNA polymerase, plays a crucial role in maintaining telomere length, which is essential for cells to overcome senescence induced by telomere shortening during DNA replication [5,7]. Telomerase activity is tightly regulated, and TERT expression is repressed in most differentiated cells but can be reactivated in cancer cells, contributing to tumorigenesis through telomere-dependent and-independent mechanisms [1,4,6].

TERT promoter mutations are highly recurrent in over 50 cancer types and are the most common mutation in many cancers [2]. These mutations upregulate TERT transcription, enabling tumor cells to achieve unlimited proliferative capacity by elongating telomeres [3]. In differentiated thyroid carcinoma, TERT-p mutations are associated with high-risk clinicopathological features and worse prognosis [3]. In CNS tumors like meningiomas, medulloblastomas, and primary glial neoplasms, TERT promoter mutations lead to up-regulation of TERT transcription, while in ependymomas and pediatric brain tumors, TERT promoter hypermethylation has the same effect [5]. In melanoma, TERT-p mutations are frequent in chronic and non-chronic sun-damage melanoma and correlate with adverse prognosis, and in acral melanoma, TERT copy number gains and gene amplification predict reduced survival [8]. In urothelial carcinomas, TERT promoter mutations and aberrant methylation play important roles in TERT transcription activation and telomerase activation, and have potential in non-invasive diagnostics, recurrence monitoring, and outcome prediction [9].

In conclusion, TERT is essential for telomere maintenance and its dysregulation, often through promoter mutations or epigenetic changes, is a key event in cancer development across multiple cancer types. The study of TERT in cancer, especially through the identification of its promoter mutations in various malignancies, provides insights into tumorigenesis mechanisms and potential biomarkers for diagnosis, prognosis, and therapeutic targets.