Topographical analysis of telomere length and correlation with genomic instability in whole mount prostatectomies

Authors

  • A.M. Joshua,

    1. Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada
    2. Division of Applied Molecular Oncology, Ontario Cancer Institute, Princess Margaret Hospital, Toronto, Ontario, Canada
    3. Department of Medical Oncology, Princess Margaret Hospital, Toronto, Ontario, Canada
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  • E. Shen,

    1. Faculty of Science, University of Western Ontario, London, Ontario, Canada
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  • M. Yoshimoto,

    1. Department of Pathology and Molecular Medicine, Kingston General Hospital, Queens University, Kingston, Ontario, Canada
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  • P. Marrano,

    1. Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada
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  • M. Zielenska,

    1. Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada
    2. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
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  • A.J. Evans,

    1. Department of Pathology, University Health Network, Toronto, Ontario, Canada
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  • T. Van der Kwast,

    1. Department of Pathology, University Health Network, Toronto, Ontario, Canada
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  • J.A. Squire PhD

    Corresponding author
    1. Department of Pathology and Molecular Medicine, Kingston General Hospital, Queens University, Kingston, Ontario, Canada
    • Department of Pathology and Molecular Medicine, Queen's University, Rm. 201e, Richardson Labs, 88 Stuart St., Kingston, Ontario, Canada K7L 3N6.
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  • No authors declare a conflict of interest.

Abstract

BACKGROUND

Many critical events in prostatic carcinogenesis appear to relate to the emergence of genomic instability. Characteristic genomic abnormalities such as 8p loss, 8q gain, trisomy 7, and PTEN microdeletions may provide selective advantages to increase neoplastic transformation. Evidence suggests that telomere dysfunction is a plausible mechanism for some of these abnormalities on the basis of the break-fusion-bridge cycle that can lead to manifestations of genomic instability.

METHODS

In this study, we correlate telomere length measured by quantitative FISH in various prostatic histologies with markers of genomic instability and immunohistochemical measures of proliferation and oxidative stress.

RESULTS

We find that telomere shortening is correlated with abnormalities on chromosome 8, but not with trisomy 7 or abnormalities of the PTEN locus. There are associations with C-MYC aberrations in stroma with greater proximity to cancer and a correlation between telomere length in a number of prostatic histologies and the adjacent stroma, suggesting the importance of microenvironmental effects on telomere maintenance in the prostate. This finding was also supported by the finding of the correlation between telomere attrition and the levels of oxidative stress as measured by malondialdehyde staining in HPIN lesions close to cancer.

CONCLUSIONS

Telomere attrition in the prostate gland is associated with particular genomic aberrations that contribute to the genomic instability characteristic of prostatic carcinogenesis. Correlations between various histologies and adjacent stroma telomere length suggest it is also may reveal microenvironmental effects within the prostate gland. Oxidative stress may contribute to telomere attrition in HPIN close to cancer. Prostate 71:778–790, 2011. © 2010 Wiley-Liss, Inc.

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