RASSF1A promoter methylation is frequently detected in both pre-malignant and non-malignant microdissected prostatic epithelial tissues

Authors

  • Alan Aitchison,

    1. Department of Oncology, University of Cambridge, Hills Road, Cambridge, United Kingdom
    Current affiliation:
    1. Uro-Oncology Group, Department of Oncology, University of Cambridge, Hills Road, Cambridge, UK, CB2 2XZ.
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  • Anne Warren,

    1. Department of Histopathology, Addenbrookes Hospital, Cambridge, United Kingdom
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  • David Neal,

    1. Uro-Oncology Group, Department of Oncology, University of Cambridge, Hills Road, Cambridge, United Kingdom
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  • Pamela Rabbitts

    Corresponding author
    1. Department of Oncology, University of Cambridge, Hills Road, Cambridge, United Kingdom
    Current affiliation:
    1. Leeds Institute for Molecular Medicine, University of Leeds, St. James's University Hospital, Leeds LS9 7TF.
    • Leeds Institute of Molecular Medicine, St James's University Hospital, Leeds, LS97TF UK.
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Abstract

Background

The RASSF1A gene is a tumor suppressor gene inactivated by hypermethylation in a very wide variety of malignant tumors including prostate cancer.

Methods

In this study we have used laser capture microdissection to provide pure cell populations to investigate the methylation status of 16 CpG sites in the promoter region of this gene in prostatic intra-epithelial neoplasia, in histologically normal epithelial cells associated with these lesions and in epithelial cells from benign prostatic hyperplasia.

Results

Unexpectedly, frequent methylation, detected by sequence analysis following bisulphite treatment, was observed in benign epithelium as well as in the lesions associated with prostatic intra-epithelial neoplasia and at high risk of cancer formation. Fifty percent or more CpG sites were methylated in 7/14 prostatic intra-epithelial neoplasms, 8/11 histologically normal epithelial cells and 8/12 specimens of benign prostatic tissue.

Conclusion

These observations suggest that methylation of the RASSF1A gene is present in both pre-malignant and benign epithelia and suggests quantitation is required for it to be an effective marker of early prostate cancer. Prostate 67: 638–644, 2007. © 2007 Wiley-Liss, Inc.

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