ArticleThe Journal of clinical investigation2021
Dual role of allele-specific DNA hypermethylation within the TERT promoter in cancer.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Biogenesis and Regulation of Telomerase during Development and Cancer.Cold Spring Harbor perspectives in biology · 2026Review
- THOR methylation as a pan-cancer mechanism ofFrontiers in oncology · 2026Review
- Epigenetics of glaucoma in the trabecular meshwork.Clinical epigenetics · 2025Review
- Long read sequencing reveals novel genomic and epigenomic alterations in repetitive regions of high grade serous ovarian cancer.Scientific reports · 2025Article
- Distinct molecular profile and outcome of oligodendroglioma, IDH-mutant, 1p/19q-codeleted, and TERTp-wildtype: A grade 1 oligodendroglioma of young patients?Neuro-oncology · 2025Article
- TERT promoter methylation predicts overall survival, immune cell infiltration and response to immunotherapy in clear cell renal cell carcinoma.Clinical epigenetics · 2025Article
- Pan-cancer analysis of the prognosis and immune infiltration of NSUN7 and its potential function in renal clear cell carcinoma.Discover oncology · 2025Article
- TERT upstream promoter methylation regulates TERT expression and acts as a therapeutic target in TERT promoter mutation-negative thyroid cancer.Cancer cell international · 2024Article
- Mechanisms of telomere maintenance and associated therapeutic vulnerabilities in malignant gliomas.Neuro-oncology · 2024Review
- Prognostic Impact ofCancers · 2024Article
- Exploring Epigenetic Modifications as Potential Biomarkers and Therapeutic Targets in Glaucoma.International journal of molecular sciences · 2024Review
- The C250T Mutation ofCancers · 2024Article
- The regulations of telomerase reverse transcriptase (TERT) in cancer.Cell death & disease · 2024Review
- Exploring the impact of diabetes on aging: insights from TERT and COL1A1 methylation.Turkish journal of biology = Turk biyoloji dergisi · 2024Article
- Targeting oncogenic TERT promoter variants by allele-specific epigenome editing.Clinical epigenetics · 2023Article
- The DNA methylation status of the TERT promoter differs between subtypes of mature B-cell lymphomas.Blood cancer journal · 2023Article
- Conserved features of TERT promoter duplications reveal an activation mechanism that mimics hotspot mutations in cancer.Nature communications · 2022Article
- Tieing together loose ends: telomere instability in cancer and aging.Molecular oncology · 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
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20 authors.
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Abstract
Aberrant activation of telomerase in human cancer is achieved by various alterations within the TERT promoter, including cancer-specific DNA hypermethylation of the TERT hypermethylated oncological region (THOR). However, the impact of allele-specific DNA methylation within the TERT promoter on gene transcription remains incompletely understood. Using allele-specific next-generation sequencing, we screened a large cohort of normal and tumor tissues (n = 652) from 10 cancer types and identified that differential allelic methylation (DAM) of THOR is restricted to cancerous tissue and commonly observed in major cancer types. THOR-DAM was more common in adult cancers, which develop through multiple stages over time, than in childhood brain tumors. Furthermore, THOR-DAM was especially enriched in tumors harboring the activating TERT promoter mutations (TPMs). Functional studies revealed that allele-specific gene expression of TERT requires hypomethylation of the core promoter, both in TPM and TERT WT cancers. However, the expressing allele with hypomethylated core TERT promoter universally exhibits hypermethylation of THOR, while the nonexpressing alleles are either hypermethylated or hypomethylated throughout the promoter. Together, our findings suggest a dual role for allele-specific DNA methylation within the TERT promoter in the regulation of TERT expression in cancer.
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