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. 2020 Dec 24;12(1):12.
doi: 10.3390/genes12010012.

MYC DNA Methylation in Prostate Tumor Tissue Is Associated with Gleason Score

Kathryn Hughes Barry  1   2 , Kareshma Mohanty  1 , Patricia A Erickson  1 , Difei Wang  3 , Jianxin Shi  3 , Gary Rose  4 , Ashley Cellini  5 , Kimberly Clark  5 , Nicholas Ambulos Jr  2   6 , Jing Yin  2   6 , Liying Yan  7 , Matthew Poulin  7 , Ann Meyer  7 , Yuji Zhang  1   2 , Søren M Bentzen  1   2 , Allen Burke  4 , Arif Hussain  2   8   9 , Sonja I Berndt  10
Affiliations

MYC DNA Methylation in Prostate Tumor Tissue Is Associated with Gleason Score

Kathryn Hughes Barry et al. Genes (Basel). .

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.

Keywords: DNA methylation; Gleason score (GS); MYC; RNA expression; aggressive disease; non-coding RNAs (ncRNAs); prostate cancer; tumor tissue biomarkers.

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Conflict of interest statement

L.Y., M.P. and A.M. are employed by EpigenDx, Inc, and L.Y. is the major stockholder of EpigenDx. All other authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure A1
Figure A1
Box plots displaying the median % DNA methylation and interquartile range (25th: 75th percentiles) by Gleason score (GS 6 vs. GS 7) for the two MYC exon 3 CpG sites evaluated in The Cancer Genome Atlas (TCGA) data, n = 293 prostate tumor samples: (a) cg00163372 and (b) cg08526705.
Figure 1
Figure 1
Study workflow for the University of Maryland samples. Abbreviations: AA, African American; CA, Caucasian.
Figure 2
Figure 2
Box plots displaying the median % DNA methylation and interquartile range (25th: 75th percentiles) for MYC CpG sites by GS in the University of Maryland prostate tumor samples (n = 89).
See this image and copyright information in PMC

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