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Chromosomal instability in ulcerative colitis is related to telomere shortening

Nature Genetics volume 32, pages 280–284 (2002)Cite this article

Abstract

Ulcerative colitis, a chronic inflammatory disease of the colon, is associated with a high risk of colorectal carcinoma1 that is thought to develop through genomic instability2. We considered that the rapid cell turnover and oxidative injury observed in ulcerative colitis might accelerate telomere shortening3, thereby increasing the potential of chromosomal ends to fuse4, resulting in cycles of chromatin bridge breakage and fusion5,6 and chromosomal instability associated with tumor cell progression7,8. Here we have used quantitative fluorescence in situ hybridization to compare chromosomal aberrations and telomere shortening in non-dysplastic mucosa taken from individuals affected by ulcerative colitis, either with (UC progressors) or without (UC non-progressors) dysplasia or cancer. Losses, but not gains, of chromosomal arms and centromeres are highly correlated with telomere shortening. Chromosomal losses are greater and telomeres are shorter in biopsy samples from UC progressors than in those from UC non-progressors or control individuals without ulcerative colitis. A mechanistic link between telomere shortening and chromosomal instability is supported by a higher frequency of anaphase bridges—an intermediate in the breakage and fusion of chromatin bridges9—in UC progressors than in UC non-progressors or control individuals. Our study shows that telomere length is correlated with chromosomal instability in a precursor of human cancer.

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Figure 1: Examples of QFISH using a PNA telomeric probe.
Figure 2: Telomere length shortening in UC progressors.
Figure 3: Chromosomal arm and centromere losses (but not gains) are related to telomere shortening.
Figure 4: Higher frequency of anaphase bridges in UC progressors.

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Acknowledgements

We thank A. Stevens, S. Dziadon and G. Martelino for technical support. This work was supported by grants from the US National Institutes of Health.

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Authors and Affiliations

  1. Department of Pathology, University of Washington, Seattle, 98195-7705, Washington, USA

    Jacintha N. O'Sullivan, Mary P. Bronner, Teresa A. Brentnall, Jennifer C. Finley, Wen-Tang Shen, Katherine A. Gollahon, David A. Crispin & Peter S. Rabinovitch

  2. Department of Medicine, University of Washington, Seattle, 98195-7705, Washington, USA

    Mary P. Bronner & Teresa A. Brentnall

  3. Department of Biostatistics, University of Washington, Seattle, 98195-7705, Washington, USA

    Scott Emerson & Mary J. Emond

  4. Department of Surgery, University of Washington, Seattle, 98195-7705, Washington, USA

    Alexander H. Moskovitz

  5. Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, 98109-1024, Washington, USA

    John D. Potter & Peter S. Rabinovitch

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  1. Jacintha N. O'Sullivan
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Correspondence to Peter S. Rabinovitch.

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O'Sullivan, J., Bronner, M., Brentnall, T. et al. Chromosomal instability in ulcerative colitis is related to telomere shortening. Nat Genet 32, 280–284 (2002). https://doi.org/10.1038/ng989

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