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    DNA Methylation in Prostate Tumor Tissue Is Associated with Gleason Score

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    Author
    Barry, Kathryn Hughes
    Mohanty, Kareshma
    Erickson, Patricia A
    Wang, Difei
    Shi, Jianxin
    Rose, Gary
    Cellini, Ashley
    Clark, Kimberly
    Ambulos, Nicholas
    Yin, Jing
    Yan, Liying
    Poulin, Matthew
    Meyer, Ann
    Zhang, Yuji
    Bentzen, Søren M
    Burke, Allen
    Hussain, Arif
    Berndt, Sonja I
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    Date
    2020-12-24
    Journal
    Genes
    Publisher
    MDPI AG
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.3390/genes12010012
    Abstract
    Increasing evidence suggests a role of epigenetic mechanisms at chromosome 8q24, an important cancer genetic susceptibility region, in prostate cancer. We investigated whether MYC DNA methylation at 8q24 (six CpG sites from exon 3 to the 3' UTR) in prostate tumor was associated with tumor aggressiveness (based on Gleason score, GS), and we incorporated RNA expression data to investigate the function. We accessed radical prostatectomy tissue for 50 Caucasian and 50 African American prostate cancer patients at the University of Maryland Medical Center, selecting an equal number of GS 6 and GS 7 cases per group. MYC DNA methylation was lower in tumor than paired normal prostate tissue for all six CpG sites (median difference: -14.74 to -0.20 percentage points), and we observed similar results for two nearby sites in The Cancer Genome Atlas (p < 0.0001). We observed significantly lower methylation for more aggressive (GS 7) than less aggressive (GS 6) tumors for three exon 3 sites (for CpG 212 (chr8:128753145), GS 6 median = 89.7%; GS 7 median = 85.8%; p-value = 9.4 × 10-4). MYC DNA methylation was not associated with MYC expression, but was inversely associated with PRNCR1 expression after multiple comparison adjustment (q-value = 0.04). Findings suggest that prostate tumor MYC exon 3 hypomethylation is associated with increased aggressiveness.
    Keyword
    DNA methylation
    Gleason score (GS)
    MYC
    RNA expression
    aggressive disease
    non-coding RNAs (ncRNAs)
    prostate cancer
    tumor tissue biomarkers
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/14321
    ae974a485f413a2113503eed53cd6c53
    10.3390/genes12010012
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