Cited by 260Telomeres, Telomerase, and SenescenceEpigenetics and DNA MethylationGenomics and Chromatin Dynamics

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Hypermethylation of the human telomerase catalytic subunit (hTERT) gene correlates with telomerase activity

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Guilleret, Isabelle, Yan, Pu, Grange, Fabienne, Braunschweig, Richard, Bosman, Fred T., Benhattar, Jean·2002·International Journal of Cancer

DOI 10.1002/ijc.10593

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Abstract

DNA methylation is an epigenetic process involved in embryonic development, differentiation and aging. It is 1 of the mechanisms resulting in gene silencing in carcinogenesis, especially in tumor suppressor genes (e.g., p16, Rb). Telomerase, the DNA polymerase adding TTAGGG repeats to the chromosome end, is involved in the regulation of the replicative life span by maintaining telomere length. This enzyme is activated in germ and stem cells, repressed in normal somatic cells and reactivated in a large majority of tumor cells. The promoter region of the hTERT gene, encoding for the catalytic subunit of human telomerase, has been located in a CpG island and may therefore be regulated at least in part by DNA methylation. We analyzed the methylation status of 27 CpG sites within the hTERT promoter core region by methylation‐sensitive single‐strand conformation analysis (MS‐SSCA) and direct sequencing using bisulfite‐modified DNA in 56 human tumor cell lines, as well as tumor and normal tissues from different organs. A positive correlation was observed among hypermethylation of the hTERT promoter, hTERT mRNA expression and telomerase activity (p < 0.00001). Furthermore, this correlation was confirmed in normal tissues where hypermethylation of the hTERT promoter was found exclusively in hTERT‐expressing telomerase‐positive samples and was absent in telomerase‐negative samples (p < 0.00002). Since tumor tissues contain also nonneoplastic stromal elements, we performed microdissection to allow confirmation that the hTERT promoter methylation truly occurred in tumor cells. Our results suggest that methylation may be involved in the regulation of hTERT gene expression. To our knowledge, this is the first gene in which methylation of its promoter sequence has been found to be positively correlated with gene expression. © 2002 Wiley‐Liss, Inc.

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Authors: Guilleret, I., Yan, P., Grange, F., Braunschweig, R., Bosman, F. T., & Benhattar, J.
Affiliations: Centre Hospitalier Universitaire Vaudois (CH)
Corresponding author: Benhattar, Jean
ORCID: Guilleret, Isabelle
Bosman, Fred T.
Benhattar, Jean
Venue: International Journal of Cancer
Publisher: Wiley
Published: 2002-08-29
Volume: 101
Issue: 4
Pages: 335-341
ISSN: 0020-7136 (ISSN-L)
1097-0215
DOI: 10.1002/ijc.10593
OpenAlex: W2055902044
Cited by: 260
References: 44
Citations by year: 2026: 3 · 2025: 5 · 2024: 10 · 2023: 13 · 2022: 12 · 2021: 12 · 2020: 18 · 2019: 13 · 2018: 12 · 2017: 12 · 2016: 19 · 2015: 18 · 2014: 5 · 2013: 12 · 2012: 8
FWCI: 4.00
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: International Journal of Cancer (publishedVersion)
PubMed (publishedVersion)
IRIS (submittedVersion)
SERVAL (Université de Lausanne) (submittedVersion)
Funders: National Science Foundation
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords: hTERT, telomerase, promoter hypermethylation, DNA methylation, CpG islands, telomerase activity, gene expression regulation, tumor suppressor, gene silencing, cancer cell lines, telomere length
MeSH terms: DNA-Binding Proteins, Humans, Neoplasms, Promoter Regions, Genetic, RNA, Messenger, Tumor Cells, Cultured, Gene Expression Regulation, Enzymologic, Polymorphism, Single-Stranded Conformational, Telomerase, DNA Methylation

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Hypermethylation of the human telomerase catalytic subunit (hTERT) gene correlates with telomerase activity

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