DNA Methylation in Prostate Tumor Tissue Is Associated with Gleason Score
Author
Barry, Kathryn HughesMohanty, 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
Date
2020-12-24Journal
GenesPublisher
MDPI AGType
Article
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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 methylationGleason score (GS)
MYC
RNA expression
aggressive disease
non-coding RNAs (ncRNAs)
prostate cancer
tumor tissue biomarkers
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http://hdl.handle.net/10713/14321ae974a485f413a2113503eed53cd6c53
10.3390/genes12010012
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