ArticleOncogene2014
Overexpression and promoter mutation of the TERT gene in malignant pleural mesothelioma.
Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.
- Clinical Characteristics and Prognostic Significance of TERT Promoter Mutations in Cancer: A Cohort Study and a Meta-Analysis.PloS one · 2016Pooled it
- NIPU: a randomised, open-label, phase II study evaluating nivolumab and ipilimumab combined with UV1 vaccination as second line treatment in patients with malignant mesothelioma.Journal of translational medicine · 2021Trial
- Telomeres and telomerase in mesothelioma: Pathophysiology, biomarkers and emerging therapeutic strategies (Review).International journal of oncology · 2025Review
- Therapeutic Strategies to Improve the Treatment of Pleural Mesothelioma.Current medicinal chemistry · 2025Review
- Telomere length andRadiology and oncology · 2024Observational
- TERT and BRAF V600E mutations in thyroid cancer of World Trade Center Responders.Carcinogenesis · 2023Article
- KRAS Mutations Are Associated with Shortened Survival in Patients with Epithelioid Malignant Pleural Mesothelioma.Cancers · 2023Article
- Deciphering the Functions of Telomerase Reverse Transcriptase in Head and Neck Cancer.Biomedicines · 2023Review
- Asbestos accelerates disease onset in a genetic model of malignant pleural mesothelioma.Frontiers in toxicology · 2023Article
- Comprehensive genomic and tumour immune profiling reveals potential therapeutic targets in malignant pleural mesothelioma.Genome medicine · 2022Article
- Genetic testing and prognosis of sarcomatoid hepatocellular carcinoma patients.Frontiers in oncology · 2022Article
- Exploring the Interplay of Telomerase Reverse Transcriptase and β-Catenin in Hepatocellular Carcinoma.Cancers · 2021Review
- Genomics and Functional Genomics of Malignant Pleural Mesothelioma.International journal of molecular sciences · 2020Review
- Genetic alterations of malignant pleural mesothelioma: association with tumor heterogeneity and overall survival.Molecular oncology · 2020Article
- Therapeutic Landscape of Malignant Pleural Mesothelioma: Collateral Vulnerabilities and Evolutionary Dependencies in the Spotlight.Frontiers in oncology · 2020Review
- The Biology of Malignant Mesothelioma and the Relevance of Preclinical Models.Frontiers in oncology · 2020Review
- The role of telomeres and telomerase in cirrhosis and liver cancer.Nature reviews. Gastroenterology & hepatology · 2019Review
- Not the same thing: metastatic PTCs have a different background than ATCs.Endocrine connections · 2018Article
- Mesotheliomas in Genetically Engineered Mice Unravel Mechanism of Mesothelial Carcinogenesis.International journal of molecular sciences · 2018Review
- Article
Corrections and comments
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Authors and funding
13 authors at 10 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Malignant pleural mesothelioma (MPM) is a very aggressive tumor with no known curative treatment. Better knowledge of the molecular mechanisms of mesothelial carcinogenesis is required to develop new therapeutic strategies. MPM, like all cancer cells, needs to maintain telomere length to prevent senescence. Previous studies suggested that the telomere lengthening mechanism in MPM is based mainly on telomerase activity. For this reason, we focused on the key catalytic enzyme, TERT (telomerase reverse transcriptase), by analyzing its gene expression in MPM and by studying the mechanism underlying its upregulation. We used our large collection of MPM composed of 61 MPM in culture and 71 frozen MPM tumor samples. Evaluation of TERT mRNA expression by quantitative RT-PCR showed overexpression in MPM in culture compared with normal mesothelial cells, and in MPM tumor samples compared with normal pleura. We identified a 'hot spot' of mutations in the TERT gene core promoter in both MPM in culture and in MPM tumor samples with an overall frequency of 15%. Furthermore, data clearly identified mutation in the TERT promoter as a mechanism of TERT mRNA upregulation in MPM. In contrast, gene copy number amplification was not associated with TERT overexpression. Then, we analyzed the clinicopathological, etiological and genetic characteristics of MPM with mutations in the TERT promoter. TERT promoter mutations were more frequent in MPM with sarcomatoid histologic subtype (P<0.01), and they were frequently associated with CDKN2A gene inactivation (P=0.03). In conclusion, a subgroup of MPM presents TERT promoter mutations, which lead to TERT mRNA upregulation. This is the first recurrent gain-of-function oncogenic mutations identified in MPM.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.