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Epigenetic regulation of telomeres in human cancer

Oncogene volume 27, pages 6817–6833 (2008)Cite this article

Abstract

Hypomethylation of repeated elements in the genome is a common feature of human cancer, however, the direct consequences of this epigenetic defect for cancer biology are still largely unknown. Telomeres are specialized chromatin structures at the ends of eukaryotic chromosomes formed by tandem repeats of G-rich sequences and associated proteins, which have an essential role in chromosome end protection and genomic stability. Telomeric DNA repeats cannot be methylated, however, the adjacent subtelomeric DNA is heavily methylated in humans. Here, we show that the methylation status of subtelomeric DNA repeats negatively correlates with telomere length and telomere recombination in a large panel of human cancer cell lines. These findings suggest that tumor telomere length and integrity can be influenced by epigenetic factors. Finally, we show that treatment of human cancer cell lines with demethylating drugs results in hypomethylation of subtelomeric repeats and increased telomere recombination, which in turn may facilitate telomere elongation. All together, these findings suggest that tumor telomere length and integrity can be influenced by the epigenetic status of cancer cells.

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Acknowledgements

EV is a predoctoral fellow of the Spanish Ministry of Education and Science (MEC). MA Blasco's Laboratory is funded by the MEC (SAF2005-00277, GEN2001-4856-C13-08), by the Regional Government of Madrid (GR/SAL/0597/2004), European Union (TELOSENS FIGH-CT-2002-00217, INTACT LSHC-CT-2003-506803, ZINCAGE FOOD-CT-2003-506850, RISC-RAD FI6R-CT-2003-508842, MOL CANCER MED LSHC-CT-2004-502943) and the Josef Steiner Cancer Research Award 2003.

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Authors and Affiliations

  1. Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Center (CNIO), Madrid, Spain

    E Vera, A Canela & M A Blasco

  2. Cancer Epigenetics Group, Molecular Pathology Program, Spanish National Cancer Center (CNIO), Madrid, Spain

    M F Fraga & M Esteller

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  1. E Vera
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  2. A Canela
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  3. M F Fraga
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  4. M Esteller
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  5. M A Blasco
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Correspondence to M A Blasco.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Vera, E., Canela, A., Fraga, M. et al. Epigenetic regulation of telomeres in human cancer. Oncogene 27, 6817–6833 (2008). https://doi.org/10.1038/onc.2008.289

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