<i>TERT</i>gene: its function and dysregulation in cancer

Colebatch, Andrew J.; Dobrovic, Alexander; Cooper, Wendy A.

doi:10.1136/jclinpath-2018-205653

Cited by 78 publications

(51 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The enrichment of various pathways and processes that are involved in telomere maintenance as well as the up-regulation of TERT gene was, in fact, observed in the group of UF NB-hop tumors. The aberrant expression of TERT has been described to be closely associated with tumorigenesis [111], and the activation of telomerase through over-expression of TERT is thought to represent the most common pathway for cellular immortalization [25]. The expression of the TERT gene has been shown to correlate with telomerase activity in experiments involving NB tumor tissues [112] and to be a prognostic marker in various adult and pediatric tumors, including NB, where high levels of telomerase expression/activity were found to predict poor outcome [113,114].…”

Section: Discussionmentioning

confidence: 99%

“…Telomerase is a complex ribonucleic reverse transcriptase that is responsible for telomere maintenance by synthesizing telomeric DNA repeats at the 3 ends of linear chromosomes [24]. The catalytic subunit of the human telomerase reverse transcriptase (TERT) is a key component of the telomerase complex and it is detectable in over 90% of human cancers [25]. Alternative lengthening of telomeres (ALT) is an intra-telomeric recombination mechanism that may be employed by tumor cells to maintain telomere lengthening independently by telomerase activation [24].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Hypoxia Predicts Poor Prognosis in Neuroblastoma Patients and Associates with Biological Mechanisms Involved in Telomerase Activation and Tumor Microenvironment Reprogramming

Cangelosi

Morini

Zanardi

et al. 2020

Cancers

View full text Add to dashboard Cite

The biological and clinical heterogeneity of neuroblastoma (NB) demands novel biomarkers and therapeutic targets in order to drive the most appropriate treatment for each patient. Hypoxia is a condition of low-oxygen tension occurring in poorly vascularized tumor tissues. In this study, we aimed to assess the role of hypoxia in the pathogenesis of NB and at developing a new clinically relevant hypoxia-based predictor of outcome. We analyzed the gene expression profiles of 1882 untreated NB primary tumors collected at diagnosis and belonging to four existing data sets. Analyses took advantage of machine learning methods. We identified NB-hop, a seven-gene hypoxia biomarker, as a predictor of NB patient prognosis, which is able to discriminate between two populations of patients with unfavorable or favorable outcome on a molecular basis. NB-hop retained its prognostic value in a multivariate model adjusted for established risk factors and was able to additionally stratify clinically relevant groups of patients. Tumors with an unfavorable NB-hop expression showed a significant association with telomerase activation and a hypoxic, immunosuppressive, poorly differentiated, and apoptosis-resistant tumor microenvironment. NB-hop defines a new population of NB patients with hypoxic tumors and unfavorable prognosis and it represents a critical factor for the stratification and treatment of NB patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hypoxia Predicts Poor Prognosis in Neuroblastoma Patients and Associates with Biological Mechanisms Involved in Telomerase Activation and Tumor Microenvironment Reprogramming

Cangelosi

Morini

Zanardi

et al. 2020

Cancers

View full text Add to dashboard Cite

show abstract

“…However, more frequently mutated than any of these genes is the TERT promoter [11][12][13][14]. TERT encodes the catalytic subunit of the telomerase complex which is upregulated in the majority of cancers and is essential for telomere maintenance and overcoming senescence [15]. Mutations in the TERT promoter at chr5:1,295,228 and chr5:1,295,250 (hg19), 124 and 146 bp upstream of the transcription start site, generate consensus binding motifs for ETS transcription factors, increasing TERT expression and activity, and are associated with worse prognosis in UBC patients [16,17].…”

Section: Introductionmentioning

confidence: 99%

Non-Coding Mutations in Urothelial Bladder Cancer: Biological and Clinical Relevance and Potential Utility as Biomarkers

Jeeta

Gordon

Baxter

et al. 2019

BLC

View full text Add to dashboard Cite

BACKGROUND & OBJECTIVE: Whole genome sequencing has identified recurrent non-coding mutations that may be important in carcinogenesis. We investigate the frequency of 5 such non-coding mutation hotspots in urothelial bladder cancers (UBCs) and assess their potential for UBC detection and prognostication. METHODS: DNA extracted from 302 UBCs was subjected to targeted next generation sequencing of non-coding mutation hotspots in GPR126, PLEKHS1, TBC1D12, LEPROTL1 and WDR74. The frequency of mutations, and associations with stage, grade, age, gender, smoking status, clinical outcomes, mutation signatures and gene expression were analysed using χ 2 tests, logistic regression and Cox proportional hazards models. RESULTS: Non-coding mutations were common across all stages and grades of UBC. The frequencies were: GPR126 53.0%, PLEKHS1 38.7%, TBC1D12 25.5%, LEPROTL1 23.8% and WDR74 17.2%. There was an average of 1.6 mutations per UBC, and 74% of UBCs harboured at least one mutation. They frequently co-occur, and commonly accompany an APOBEC mutational signature. The mutations are not strongly associated with clinical parameters and are, most likely, early events in the development of UBC. CONCLUSIONS: Mutations at these 5 non-coding hotspots are common in UBC. Due to their high frequency across stages and grades of disease, they should be included in UBC diagnostic biomarker panels.

show abstract

“…Human telomerase reverse transcriptase has been described as a key factor that contributes to immortalization of human cancer by maintaining telomere length and genome integrity . Our results showed that YAP has a positive effect on hTERT expression, telomerase activity, and telomere maintenance, supporting for its tumor‐promoting role.…”

Section: Discussionmentioning

confidence: 99%

Human telomerase reverse transcriptase is a novel target of Hippo‐YAP pathway

et al. 2020

View full text Add to dashboard Cite

Telomerase plays a pivotal role in tumorigenesis by maintaining telomere homeostasis, a hallmark of cancer. However, the mechanisms by which telomerase is reactivated or upregulated during tumorigenesis remain incompletely understood. Here, we report that the Hippo pathway effector Yes‐associated protein (YAP) regulates the expression of human telomerase reverse transcriptase (hTERT). Ectopic expression or physiological activation of YAP increases hTERT expression, whereas knockdown of YAP decreases the expression of hTERT. YAP binds to the hTERT promoter through interaction with the TEA domain family transcription factors and activates hTERT transcription. Furthermore, sustained YAP hyperactivation promotes telomerase activity and extends telomere length, with increased hTERT expression. In addition, we show that hTERT expression is positively correlated with YAP activation in human liver cancer tissues. Together, our results demonstrate that YAP promotes hTERT expression, which could contribute to tumor progression.

show abstract

TERTgene: its function and dysregulation in cancer

Cited by 78 publications

References 64 publications

Hypoxia Predicts Poor Prognosis in Neuroblastoma Patients and Associates with Biological Mechanisms Involved in Telomerase Activation and Tumor Microenvironment Reprogramming

Hypoxia Predicts Poor Prognosis in Neuroblastoma Patients and Associates with Biological Mechanisms Involved in Telomerase Activation and Tumor Microenvironment Reprogramming

Non-Coding Mutations in Urothelial Bladder Cancer: Biological and Clinical Relevance and Potential Utility as Biomarkers

Human telomerase reverse transcriptase is a novel target of Hippo‐YAP pathway

Contact Info

Product

Resources

About