The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
Hypermethylation of the human telomerase catalytic subunit (hTERT) gene correlates with telomerase activity
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“There is a strong correlation between hTERT expression and TA, and recent studies have linked hTERT promoter hypermethylation to CRC and other cancer types [206].”
From Current and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy (2024) · cites this paper as [206]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands.
Herman, J. G., Graff, J. R., Myöhänen, S., Nelkin, B. D., & Baylin, S. B. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.18.9821 · Cited by 5,634
Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription
Jones, P. L., Veenstra, G. J. C., Wade, P. A., Vermaak, D., Kass, S. U., Landsberger, N., Strouboulis, J., & Wolffe, A. P. (1998) · Nature Genetics · doi:10.1038/561 · Cited by 2,791
Alterations in DNA Methylation: A Fundamental Aspect of Neoplasia
Baylln, S. B., Herman, J. G., Graff, J. R., Vertino, P. M., & Issa, J. J. (1997) · Advances in cancer research · doi:10.1016/s0065-230x(08)60702-2 · Cited by 1,919
MeCP2 Is a Transcriptional Repressor with Abundant Binding Sites in Genomic Chromatin
Nan, X., Campoy, F. J., & Bird, A. P. (1997) · Cell · doi:10.1016/s0092-8674(00)81887-5 · Cited by 1,288
Weinrich, S. L., Pruzan, R., Ma, L., Ouellette, M. M., Tesmer, V. M., Holt, S. E., Bodnar, A. G., Lichtsteiner, S., Kim, N. W., Trager, J. B., et al. (1997) · Nature Genetics · doi:10.1038/ng1297-498 · Cited by 975
The essentials of DNA methylation
Bird, A. (1992) · Cell · doi:10.1016/0092-8674(92)90526-i · Cited by 948
Direct activation of TERT transcription by c-MYC
Wu, K.-J., Grandori, C., Amacker, M., Simon-Vermot, N., Polack, A., Lingner, J., & Dalla-Favera, R. (1999) · Nature Genetics · doi:10.1038/6010 · Cited by 893
Telomere maintenance by recombination in human cells
Dunham, M. A., Neumann, A. A., Fasching, C. L., & Reddel, R. R. (2000) · Nature Genetics · doi:10.1038/82586 · Cited by 879
DNA methylation inhibits transcription indirectly via a methyl-CpG binding protein
Boyes, J., & Bird, A. P. (1991) · Cell · doi:10.1016/0092-8674(91)90267-3 · Cited by 733
High levels of De Novo methylation and altered chromatin structure at CpG islands in cell lines
Antequera, F., Boyes, J., & Bird, A. P. (1990) · Cell · doi:10.1016/0092-8674(90)90015-7 · Cited by 696
Takakura, M., Kyo, S., Kanaya, T., Hirano, H., Takeda, J., Yutsudo, M., & Inoue, M. (1999) · PubMed · Cited by 599
Methylation-Sensitive Sequence-Specific DNA Binding by the c-Myc Basic Region
Prendergast, G. C., & Ziff, E. B. (1991) · Science · doi:10.1126/science.1987636 · Cited by 578
Estrogen activates telomerase.
Kyo, S., Takakura, M., Kanaya, T., Zhuo, W., FUJIMOTO, K., Nishio, Y., Orimo, A., & Inoue, M. (1999) · PubMed · Cited by 509
Cong, Y. (1999) · Human Molecular Genetics · doi:10.1093/hmg/8.1.137 · Cited by 485
高倉, 正. (2002) · Medical Entomology and Zoology · Cited by 475
Cloning and characterization of the promoter region of human telomerase reverse transcriptase gene.
Horikawa, I., Cable, P. L., Afshari, C. A., & Barrett, J. C. (1999) · PubMed · Cited by 393
Investigating stem cells in human colon by using methylation patterns
Yatabe, Y., Tavaré, S., & Shibata, D. K. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.191225998 · Cited by 368
Forsyth, N. R., Wright, W. E., & Shay, J. W. (2002) · Differentiation · doi:10.1046/j.1432-0436.2002.690412.x · Cited by 345
Telomeres and telomerase in aging and cancer
Harley, C. (1995) · Current Opinion in Genetics & Development · doi:10.1016/0959-437x(95)80016-6 · Cited by 322
Zingg, J.-M. A. (1997) · Carcinogenesis · doi:10.1093/carcin/18.5.869 · Cited by 321
Activity, function, and gene regulation of the catalytic subunit of telomerase (hTERT)
Poole, J. C., Andrews, L. G., & Tollefsbol, T. O. (2001) · Gene · doi:10.1016/s0378-1119(01)00440-1 · Cited by 280
Studies of the molecular mechanisms in the regulation of telomerase activity
Liu, J. (1999) · The FASEB Journal · doi:10.1096/fasebj.13.15.2091 · Cited by 254
Hypermethylation of tumor suppressor genes in cancer
Herman, J. G. (1999) · Seminars in Cancer Biology · doi:10.1006/scbi.1999.0138 · Cited by 225
Devereux, T. R., Horikawa, I., Anna, C. H., Annab, L. A., Afshari, C. A., & Barrett, J. C. (1999) · PubMed · Cited by 215
A Bisulfite Method of 5-Methylcytosine Mapping That Minimizes Template Degradation
Raizis, A. M., Schmitt, F., & Jost, J. P. (1995) · Analytical Biochemistry · doi:10.1006/abio.1995.1204 · Cited by 212
Methylation of the human telomerase gene CpG island.
Dessain, S. K., Yu, H., Reddel, R. R., Beijersbergen, R. L., & Weinberg, R. A. (2000) · PubMed · Cited by 185
Tahara, H., Yasui, W., Tahara, E., Fujimoto, J., Ito, K., Tamai, K., Nakayama, J., Ishikawa, F., Tahara, E., & Ide, T. (1999) · Oncogene · doi:10.1038/sj.onc.1202458 · Cited by 151
DNA Methylation from Embryo to Adult
Razin, A., & Kafri, T. (1994) · Progress in nucleic acid research and molecular biology · doi:10.1016/s0079-6603(08)60853-3 · Cited by 129
Cook, N. R., Stampfer, M. J., Ma, J., Manson, J. E., Sacks, F. M., Buring, J. E., & Hennekens, C. H. (1999) · Cancer · doi:10.1002/(sici)1097-0142(19991101)86:9 · Cited by 121
DNA methylation analysis a review of current methodologies
Oakeley, E. J. (1999) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(99)00043-1 · Cited by 106
Serum interleukin-10 levels in patients with advanced gastrointestinal malignancies
Vita, F. D., Orditura, M., Galizia, G., Romano, C. P., Infusino, S., Auriemma, A., Lieto, E., & Catalano, G. (1999) · Cancer · doi:10.1002/(sici)1097-0142(19991115)86:10 · Cited by 93
Oh, S., Song, Y., Kim, U.-J., Yim, J., & Kim, T. K. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.1366 · Cited by 71
Battistuzzi, G., D’Urso, M., Toniolo, D., Persico, G. M., & Luzzatto, L. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.5.1465 · Cited by 68
Studies of DNA methylation in animals
Bird, A. P., Tate, P. H., Nan, X., Campoy, J., Meehan, R. R., Cross, S. H., Tweedie, S., Charlton, J., & Macleod, D. (1995) · Journal of Cell Science · doi:10.1242/jcs.1995.supplement_19.5 · Cited by 66
Bednarik, D. P., Duckett, C. S., Kim, S. U., Perez, V. L., Griffis, K., Guenthner, P. C., & Folks, T. M. (1991) · PubMed · Cited by 62
The composition of CD34 subpopulations differs between bone marrow, blood and cord blood.
Fritsch, G., Stimpfl, M., Kurz, M., Printz, D., Buchinger, P., Fischmeister, G., Hoecker, P., & Gadner, H. (1996) · PubMed · Cited by 61
Yan, P., Coindre, J., Benhattar, J., Bosman, F. T., & Guillou, L. (1999) · PubMed · Cited by 54
Self-citationChaubert, P., Bautista, D., & Benhattar, J. (1993) · PubMed · Cited by 49
Self-citationBian, Y.-S., Yan, P., Osterheld, M. C., Fontolliet, C., & Benhattar, J. (2001) · BioTechniques · doi:10.2144/01301st02 · Cited by 46
Self-citationCell proliferation, carcinogenesis and diverse mechanisms of telomerase regulation
Krupp, G., Klapper, W., & Parwaresch, R. M. (2000) · Cellular and Molecular Life Sciences · doi:10.1007/pl00000708 · Cited by 36
FOCAL INTRATUMORAL HETEROGENEITY FOR TELOMERASE ACTIVITY IN HUMAN PROSTATE CANCER
Wullich, B., Rohde, V., Oehlenschlager, B., Bonkhoff, H., Ketter, R., Zwergel, T., & Sattler, H.-P. (1999) · The Journal of Urology · doi:10.1016/s0022-5347(05)68872-6 · Cited by 34
Baïsse, B., Bia, Y.-S., & Benhattar, J. (2000) · BioTechniques · doi:10.2144/00285bm06 · Cited by 32
Self-citationHermann, R., & Doerfler, W. (1991) · FEBS Letters · doi:10.1016/0014-5793(91)80391-f · Cited by 31
Tissue Quality is an Important Determinant of Telomerase Activity as Measured by TRAP Assay
Yan, P., Bosman, F. T., & Benhattar, J. (1998) · BioTechniques · doi:10.2144/98254dt05 · Cited by 28
Self-citation
Cited by
Sorted by citations
Folate and DNA Methylation: A Review of Molecular Mechanisms and the Evidence for Folate's Role
Crider, K. S., Yang, T. P., Berry, R. J., & Bailey, L. B. (2012) · Advances in Nutrition · doi:10.3945/an.111.000992 · Cited by 1,055
The relationship between COPD and lung cancer
Durham, A. L., & Adcock, I. M. (2015) · Lung Cancer · doi:10.1016/j.lungcan.2015.08.017 · Cited by 456
Sulforaphane Causes Epigenetic Repression of hTERT Expression in Human Breast Cancer Cell Lines
Meeran, S. M., Patel, S. N., & Tollefsbol, T. O. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011457 · Cited by 372
Understanding and exploiting hTERT promoter regulation for diagnosis and treatment of human cancers
Kyo, S., Takakura, M., Fujiwara, T., & Inoue, M. (2008) · Cancer Science · doi:10.1111/j.1349-7006.2008.00878.x · Cited by 347
TERT—Regulation and Roles in Cancer Formation
Dratwa, M., Wysoczańska, B., Łacina, P., Kubik, T., & Bogunia‐Kubik, K. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.589929 · Cited by 331
Metadata
- Authors
- Guilleret, I., Yan, P., Grange, F., Braunschweig, R., Bosman, F. T., & Benhattar, J.
- Affiliations
- Centre Hospitalier Universitaire Vaudois (CH)
- Corresponding author
- 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
- 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
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
