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Identification of a unique epigenetic sub-microenvironment in prostate cancer

  1. Author:
    Rodriguez-Canales, J.
    Hanson, J. C.
    Tangrea, M. A.
    Erickson, H. S.
    Albert, P. S.
    Wallis, B. S.
    Richardson, A. M.
    Pinto, P. A.
    Linehan, W. M.
    Gillespie, J. W.
    Merin, M. J.
    Libutti, S. K.
    Woodson, K. G.
    Emmert-Buck, M. R.
    Chuaqui, R. F.
  2. Author Address

    NCI, NIH, Pathogenet Unit, Pathol Lab,Adv Technol Ctr,Ctr Canc Res, Gaithersburg, MD 20877 USA. NCI, NIH, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, NIH, Biometr Res Branch, Canc Res Ctr, Bethesda, MD 20892 USA. NCI, NIH, Urol Oncol Branch, Canc Res Ctr, Bethesda, MD 20892 USA. Sci Applicat Int Corp, Frederick, MD USA. NCI, NIH, Pathol Lab, Canc Res Ctr, Bethesda, MD 20892 USA. NCI, NIH, Surg Branch, Ctr Canc Res, Bethesda, MD 20892 USA.;Emmert-Buck, MR, NCI, NIH, Pathogenet Unit, Pathol Lab,Adv Technol Ctr,Ctr Canc Res, Rm 109D,8717 Grovemont Circle, Gaithersburg, MD 20877 USA.;buckm@mail.nih.gov
    1. Year: 2007
    2. Date: Mar
  1. Journal: Journal of Pathology
    1. 211
    2. 4
    3. Pages: 410-419
  2. Type of Article: Article
  3. ISSN: 0022-3417
  1. Abstract:

    The glutathione S-transferase P1 (GSTP1) gene promoter is methylated in tumour cells in more than 90% of prostate carcinomas. Recently, GSTP1 promoter methylation was identified in tumour-associated stromal cells in addition to the tumour epithelium. To define the extent and location of stromal methylation, epigenetic mapping using pyrosequencing quantification of GSTP1 promoter methylation and an anatomical three-dimensional reconstruction of an entire human prostate specimen with cancer were performed. Normal epithelium and stroma, tumour epithelium, and tumour-associated stromal cells were laser capture-microdissected from multiple locations throughout the gland. As expected, the GSTP1 promoter in both normal epithelium and normal stromal cells distant from the tumour was not methylated and the tumour epithelium showed consistently high levels of promoter methylation throughout. However, tumour-associated stromal cells were found to be methylated only in a localized and distinct anatomical sub-field of the tumour, revealing the presence of an epigenetically unique microenvironment within the cancer. Morphologically, the sub-field consisted of typical, non-reactive stroma, representing a genomic alteration in cells that appeared otherwise histologically normal. Similar epigenetic anatomical mapping of a control prostate gland without cancer showed low background methylation levels in all cell types throughout the specimen. These data suggest that stromal cell methylation can occur in a distinct sub-region of prostate cancer and may have implications for understanding tumour biology and clinical intervention. Published in 2007 by John Wiley & Sons, Ltd.

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External Sources

  1. DOI: 10.1002/path.2133
  2. WOS: 000244615000004

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