Mutation of the TERT promoter leads to poor prognosis of patients with non-small cell lung cancer

Abstract

Abstract. Mutations in the promoter region of telomerase reverse transcriptase (TERT) and alterations in telomere length (TL) have been the focus of research in various types of cancer. In the present study, the frequency and clinical characteristics of TERT promoter mutations and TL were studied in non-small cell lung cancers (NSCLC). TERT promoter mutations and TL were analyzed in 188 patients using DNA sequencing and the reverse transcription-quantitative polymerase chain reaction, respectively. The TERT promoter mutation rate was observed to be 2.2% (4/188 NSCLC cases), and it was significantly associated with regional lymph node invasion (P<0.001). No significant difference in TL was observed between the patients with and without TERT promoter mutations. TL was decreased in males (P=0.058 vs. females) and smokers (P=0.008 vs. non-smokers). Survival analyses demonstrated poor prognoses for patients with NSCLC with TERT promoter mutations (P<0.001). Multivariate survival analyses demonstrated that TERT promoter mutations were an independent prognostic marker for poor overall survival (P=0.045). The results of the present study demonstrated that TERT promoter mutation was not frequent in NSCLC; however, it may have value as a prognostic marker in NSCLC.

Genomic and human papillomavirus profiling of an oral cancer cohort identifies TP53 as a predictor of overall survival

“…Tumors carrying activating mutations in the TERT promoter region tend to be more aggressive, both in head and neck and other cancer types [12, 27–31]. Evidence exists to suggest that these mutations are overrepresented in patients failing their first line of treatment [12].…”

AAV9-mediated telomerase activation does not accelerate tumorigenesis in the context of oncogenic K-Ras-induced lung cancer

“…In contrast to telomere shortening in healthy cells, the majority of cancer cells aberrantly reactivate telomerase to achieve unlimited proliferative potential, one of the hallmarks of cancer [ 65 ]. Indeed, many different human cancer types show mutations in either the promotor region or coding regions of the telomerase catalytic subunit TERT gene [ 23 – 31 , 66 ]. Also, a wide variety of mouse cancers activate telomerase [ 32 – 34 ].…”

“…Interestingly, owing to its ability to confer unlimited proliferative potential, TERT is also found over-expressed and mutated in the vast majority of human cancers including lung cancer where it is thought to allow cancer cell growth by ensuring a minimal telomere length to warrant telomere protection [ 23 – 31 ]. Telomerase is also upregulated in mouse tumors [ 32 – 34 ].…”

Clinical Management of Ocular Surface Squamous Neoplasia: A Review of the Current Evidence

“…However, one of the key events reported are mutations affecting the tumor suppressor gene p53, with a high percentage of CC > TT alterations, which confirms the causative role of solar rays in the etiology of the tumor [ 50 ]. Moreover, Scholz et al identified mutations in the telomerase reverse transcriptase (TERT) gene promoter—a marker of other systemic cancers [ 51 ] and a sign of worse prognosis [ 52 , 53 ]—in 44% of the 48 samples of conjunctival OSSN included in their study [ 54 ]. Finally, hyper-expression of matrix metalloproteinases MMP-9 and MMP-11 and hypo-expression of clusterin seem to be a hallmark in the tumor cell transcriptome [ 55 ].…”