Global histone modification patterns predict risk of prostate cancer recurrence View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2005-06

AUTHORS

David B. Seligson, Steve Horvath, Tao Shi, Hong Yu, Sheila Tze, Michael Grunstein, Siavash K. Kurdistani

ABSTRACT

Aberrations in post-translational modifications of histones have been shown to occur in cancer cells but only at individual promoters; they have not been related to clinical outcome. Other than being targeted to promoters, modifications of histones, such as acetylation and methylation of lysine and arginine residues, also occur over large regions of chromatin including coding regions and non-promoter sequences, which are referred to as global histone modifications. Here we show that changes in global levels of individual histone modifications are also associated with cancer and that these changes are predictive of clinical outcome. Through immunohistochemical staining of primary prostatectomy tissue samples, we determined the percentage of cells that stained for the histone acetylation and dimethylation of five residues in histones H3 and H4. Grouping of samples with similar patterns of modifications identified two disease subtypes with distinct risks of tumour recurrence in patients with low-grade prostate cancer. These histone modification patterns were predictors of outcome independently of tumour stage, preoperative prostate-specific antigen levels, and capsule invasion. Thus, widespread changes in specific histone modifications indicate previously undescribed molecular heterogeneity in prostate cancer and might underlie the broad range of clinical behaviour in cancer patients. More... »

PAGES

1262

References to SciGraph publications

Journal

TITLE

Nature

ISSUE

7046

VOLUME

435

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature03672

    DOI

    http://dx.doi.org/10.1038/nature03672

    DIMENSIONS

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/15988529


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