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Evidence for an alternative mechanism for maintaining telomere length in human tumors and tumor-derived cell lines

Nature Medicine volume 3, pages 1271–1274 (1997)Cite this article

Abstract

The gradual loss of DNA from the ends of telomeres has been implicated in the control of cellular proliferative potential1–3. Telomerase is an enzyme that restores telomeric DNA sequences4, and expression of its activity was thought to be essential for the immortalization of human cells, both in vitro and in tumor progression in vivo5. Telomerase activity has been detected in 50–100% of tumors of different types, but not in most normal adult somatic tissues6,7. It has also been detected in about 70% of human cell lines immortalized in vitro and in all tumor-derived cell lines examined to date7. It has previously been shown that in vitro immortalized telomerase-negative cell lines acquire very long and heterogeneous telomeres in association with immortalization8–11 presumably via one or more novel telomere-lengthening mechanisms that we refer to as ALT (alternative lengthening of telomeres)11. Here we report evidence for the presence of ALT in a subset of tumor-derived cell lines and tumors. The maintenance of telomeres by a mechanism other than telomerase, even in a minority of cancers, has major implications for therapeutic uses of telomerase inhibitors.

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Authors and Affiliations

  1. Children's Medical Research Institute, 214 Hawkesbury Road, Westmead, Sydney, NSW, 2145, Australia

    Tracy M. Bryan, Anna Englezou, Melissa A. Dunham & Roger R. Reddel

  2. The New Children's Hospital, Westmead, NSW, 2145, Australia

    Luciano Dalla-Pozza

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  1. Tracy M. Bryan
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  2. Anna Englezou
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  4. Melissa A. Dunham
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  5. Roger R. Reddel
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Correspondence to Roger R. Reddel.

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Bryan, T., Englezou, A., Dalla-Pozza, L. et al. Evidence for an alternative mechanism for maintaining telomere length in human tumors and tumor-derived cell lines. Nat Med 3, 1271–1274 (1997). https://doi.org/10.1038/nm1197-1271

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