ArticlePloS one2020
Interplay between TERT promoter mutations and methylation culminates in chromatin accessibility and TERT expression.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 27 citations in OpenAlex.
- Lidocaine inhibits hepatocellular carcinoma cell proliferation, migration, and invasion through the downregulation of SLC6A3.Scientific reports · 2026Article
- Epigenetics of Malignant Melanoma: Mechanisms, Diagnostic Approaches and Therapeutic Applications.Oncology research · 2026Review
- TERT Immunohistochemistry in Thin Melanomas Compared to Melanocytic Nevi.Diagnostics (Basel, Switzerland) · 2025Article
- Digital PCR-based genetic profiling from vitreous fluid as liquid biopsy for primary uveal melanoma: a proof-of-concept study.Journal of experimental & clinical cancer research : CR · 2025Article
- TERT-TP53 mutations: a novel biomarker pair for hepatocellular carcinoma recurrence and prognosis.Scientific reports · 2025Article
- The TERT Promoter is Polycomb-Repressed in Neuroblastoma Cells with Long Telomeres.Cancer research communications · 2024Article
- Pan-cancer analysis of telomere maintenance mechanisms.The Journal of biological chemistry · 2024Article
- The C250T Mutation ofCancers · 2024Article
- Pan-cancer experimental characteristic of human transcriptional patterns connected with telomerase reverse transcriptase (Frontiers in genetics · 2024Article
- Regulation and clinical potential of telomerase reverse transcriptase (TERT/hTERT) in breast cancer.Cell communication and signaling : CCS · 2023Review
- Article
- Skin Cancer Research Goes Digital: Looking for Biomarkers within the Droplets.Journal of personalized medicine · 2022Review
- The expression level of chicken telomerase reverse transcriptase in tumors induced by ALV-J is positively correlated with methylation and mutation of its promoter region.Veterinary research · 2022Article
- Direct comparison of the next-generation sequencing and iTERT PCR methods for the diagnosis of TERT hotspot mutations in advanced solid cancers.BMC medical genomics · 2022Article
- MiR-138-5p Suppresses Cell Growth and Migration in Melanoma by Targeting Telomerase Reverse Transcriptase.Genes · 2021Article
- Integrated evaluation of telomerase activation and telomere maintenance across cancer cell lines.eLife · 2021Article
- TERT Gene Fusions Characterize a Subset of Metastatic Leydig Cell Tumors.Clinical genitourinary cancer · 2021Article
- Telomerase Reverse Transcriptase (TERT) Regulation in Thyroid Cancer: A Review.Frontiers in endocrinology · 2020Review
- TERT-Regulation and Roles in Cancer Formation.Frontiers in immunology · 2020Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The telomerase reverse transcriptase (TERT) gene is responsible for telomere maintenance in germline and stem cells, and is re-expressed in 90% of human cancers. CpG methylation in the TERT promoter (TERTp) was correlated with TERT mRNA expression. Furthermore, two hotspot mutations in TERTp, dubbed C228T and C250T, have been revealed to facilitate binding of transcription factor ETS/TCF and subsequent TERT expression. This study aimed to elucidate the combined contribution of epigenetic (promoter methylation and chromatin accessibility) and genetic (promoter mutations) mechanisms in regulating TERT gene expression in healthy skin samples and in melanoma cell lines (n = 61). We unexpectedly observed that the methylation of TERTp was as high in a subset of healthy skin cells, mainly keratinocytes, as in cutaneous melanoma cell lines. In spite of the high promoter methylation fraction in wild-type (WT) samples, TERT mRNA was only expressed in the melanoma cell lines with either high methylation or intermediate methylation in combination with TERT mutations. TERTp methylation was positively correlated with chromatin accessibility and TERT mRNA expression in 8 melanoma cell lines. Cooperation between epigenetic and genetic mechanisms were best observed in heterozygous mutant cell lines as chromosome accessibility preferentially concerned the mutant allele. Combined, these results suggest a complex model in which TERT expression requires either a widely open chromatin state in TERTp-WT samples due to high methylation throughout the promoter or a combination of moderate methylation fraction/chromatin accessibility in the presence of the C228T or C250T mutations.
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