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Telomere dysfunction and the initiation of genome instability

Nature Reviews Cancer volume 3, pages 623–627 (2003)Cite this article

Abstract

Tumour growth is an evolutionary process that is characterized by the selection of clonal populations of cells that acquire distinct genetic changes. Many cancer therapies aim to exploit the specific changes that occur in cancer cells, but understanding the underlying mechanisms of genomic instability that cause these mutations could lead to more effective therapies. If common mechanisms exist for initiating genomic instability in tumours, selection could explain the differences in specific gene mutations that accumulate in different tumour types. The cause of genomic instability in human tumours is unclear, although there is evidence to indicate that telomere dysfunction could make an important contribution.

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Figure 1: Telomere shortening in a simplified cancer-progression model.
Figure 2: Model for the mechanisms by which dysfunctional telomeres contribute to genomic instability.
Figure 3: Telomere fluorescence in situ hybridization in a tissue section of colonic mucosa.

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Acknowledgements

We thank members of the Greider lab for reading the manuscript and A. I. Meeker for providing the image in figure 3. This work is supported by grants from the National Institutes of Health.

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Authors and Affiliations

  1. part of the Predoctoral Training Program in Human Genetics and Molecular Biology, Johns Hopkins University School of Medicine, 617 Hunterian Building, 725 N. Wolfe Street, Baltimore, 21205, Maryland, USA

    David M. Feldser & Jennifer A. Hackett

  2. the Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, 617 Hunterian Building, 725 N. Wolfe Street, Baltimore, 21205, Maryland, USA

    Carol W. Greider

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  1. David M. Feldser
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  2. Jennifer A. Hackett
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  3. Carol W. Greider
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Correspondence to Carol W. Greider.

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Feldser, D., Hackett, J. & Greider, C. Telomere dysfunction and the initiation of genome instability. Nat Rev Cancer 3, 623–627 (2003). https://doi.org/10.1038/nrc1142

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