Journal of Cellular Biochemistry

GSTP1 CpG island hypermethylation as a molecular biomarker for prostate cancer

Authors

  • Masashi Nakayama,

    1. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231
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  • Mark L. Gonzalgo,

    1. Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231
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  • Srinivasan Yegnasubramanian,

    1. Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231
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  • Xiaohui Lin,

    1. Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231
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  • Angelo M. De Marzo,

    1. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231
    2. Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231
    3. Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231
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  • William G. Nelson

    Corresponding author
    1. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231
    2. Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231
    3. Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231
    • Bunting-Blaustein Cancer Research Building, Room 151, 1650 Orleans Street, Baltimore, MD 21231.
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Abstract

Somatic hypermethylation of CpG island sequences at GSTP1, the gene encoding the π-class glutathione S-transferase, appears to be characteristic of human prostatic carcinogenesis. To consider the potential utility of this epigenetic alteration as a biomarker for prostate cancer, we present here a comprehensive review of the literature describing somatic GSTP1 changes in DNA from prostate cells and tissues. GSTP1 CpG island hypermethylation has been detected in prostate cancer DNA using a variety of assay techniques, including (i) Southern blot analysis (SB), after treatment with 5-mC-sensitive restriction endonucleases, (ii) the polymerase chain reaction, following treatment with 5-mC-sensitive restriction endonucleases (RE-PCR), (iii) bisulfite genomic sequencing (BGS), and (iv) bisulfite modification followed by the polymerase chain reaction, using primers selective for target sequences containing 5-mC (MSP). In the majority of the case series so far reported, GSTP1 CpG island hypermethylation was present in DNA from at least 90% of prostate cancer cases. When analyses have been carefully conducted, GSTP1 CpG island hypermethylation has not been found in DNA from normal prostate tissues, or from benign prostatic hyperplasia (BPH) tissues, though GSTP1 CpG island hypermethylation changes have been detected in DNA from candidate prostate cancer precursor lesions proliferative inflammatory atrophy (PIA) and prostatic intraepithelial neoplasia (PIN). Using PCR methods, GSTP1 CpG island hypermethylation has also been detected in urine, ejaculate, and plasma from men with prostate cancer. GSTP1 CpG island hypermethylation, a somatic epigenetic alteration, appears poised to serve as a molecular biomarker useful for prostate cancer screening, detection, and diagnosis. © 2003 Wiley-Liss, Inc.

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