ArticleThe Journal of clinical investigation2019
DNA hypermethylation within TERT promoter upregulates TERT expression in cancer.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 120 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
120 citing papers in PubMed, 1 synthesis or guideline pooled it, 186 citations in OpenAlex.
- DNA methylation as a predictor of pituitary neuroendocrine tumour behaviour: A systematic review.Journal of neuroendocrinology · 2026Pooled it
- Urine DNA methylation assay enables early detection and recurrence monitoring for bladder cancer.The Journal of clinical investigation · 2020Trial
- Special Issue "Epigenetic Genes, Biomarkers and Immunotherapy in Cancers".International journal of molecular sciences · 2026Article
- Biogenesis and Regulation of Telomerase during Development and Cancer.Cold Spring Harbor perspectives in biology · 2026Review
- Telomeric Ends and Telomerase-Canonical and Non-Canonical Roles in Breast Cancer Tumorigenesis and Therapy Resistance.Biomedicines · 2026Review
- Epigenetics of Malignant Melanoma: Mechanisms, Diagnostic Approaches and Therapeutic Applications.Oncology research · 2026Review
- A Darwinian Perspective on Tumor Evolution.International journal of biological sciences · 2026Review
- THOR methylation as a pan-cancer mechanism ofFrontiers in oncology · 2026Review
- Large-scale drug sensitivity, gene dependency, and proteogenomic analyses of telomere maintenance mechanisms in cancer cells.Nature communications · 2025Article
- Cancer and Aging Biomarkers: Classification, Early Detection Technologies and Emerging Research Trends.Biosensors · 2025Review
- A Case of Multicentric Isocitrate Dehydrogenase-Wildtype Glioblastoma With Divergent Clonal Evolution.Cureus · 2025Article
- Long read sequencing reveals novel genomic and epigenomic alterations in repetitive regions of high grade serous ovarian cancer.Scientific reports · 2025Article
- Effect of aging and exercise on hTERT expression in thymus tissue of hTERT transgenic bacterial artificial chromosome mice.GeroScience · 2025Article
- A Review on the Role of DNA Methylation in Aortic Disease Associated With Marfan Syndrome.Cardiology research · 2025Review
- TERT promoter methylation predicts overall survival, immune cell infiltration and response to immunotherapy in clear cell renal cell carcinoma.Clinical epigenetics · 2025Article
- Methylation Status of the Telomerase Reverse Transcriptase Promoter in Parotid Tumours and Adjacent Parotid Gland Tissue: A Pilot Study on the Implications for Recurrence and Development of Malignancy.Current oncology (Toronto, Ont.) · 2025Article
- EXT1 and Its Methylation Involved in the Progression of Uterine Corpus Endometrial Carcinoma Pathogenesis.Applied biochemistry and biotechnology · 2025Article
- Development of 3D Cell-Based Fluorescent Reporter Assay for Screening of Drugs Downregulating Telomerase Reverse Transcriptase.Bioengineering (Basel, Switzerland) · 2025Article
- Telomeres, telomerase, and cancer: mechanisms, biomarkers, and therapeutics.Experimental hematology & oncology · 2025Review
- Telomerase in cancer- ongoing quest and future discoveries.Molecular biology reports · 2025Review
60 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
36 authors at 12 institutions in 6 countries.
Funding
Abstract
Replicative immortality is a hallmark of cancer cells governed by telomere maintenance. Approximately 90% of human cancers maintain their telomeres by activating telomerase, driven by the transcriptional upregulation of telomerase reverse transcriptase (TERT). Although TERT promoter mutations (TPMs) are a major cancer-associated genetic mechanism of TERT upregulation, many cancers exhibit TERT upregulation without TPMs. In this study, we describe the TERT hypermethylated oncological region (THOR), a 433-bp genomic region encompassing 52 CpG sites located immediately upstream of the TERT core promoter, as a cancer-associated epigenetic mechanism of TERT upregulation. Unmethylated THOR repressed TERT promoter activity regardless of TPM status, and hypermethylation of THOR counteracted this repressive function. THOR methylation analysis in 1,352 human tumors revealed frequent (>45%) cancer-associated DNA hypermethylation in 9 of 11 (82%) tumor types screened. Additionally, THOR hypermethylation, either independently or along with TPMs, accounted for how approximately 90% of human cancers can aberrantly activate telomerase. Thus, we propose that THOR hypermethylation is a prevalent telomerase-activating mechanism in cancer that can act independently of or in conjunction with TPMs, further supporting the utility of THOR hypermethylation as a prognostic biomarker.
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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.