A Novel Approach to Assay DNA Methylation in Prostate Cancer
Technical Report,30 Sep 2013,29 Sep 2017
Northwestern University Chicago United States
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Previous studies of DNA methylation at 5-position of cytosine 5mC have led to the discovery of useful methylation biomarkers for prostate cancer diagnosis and prognosis, some of which are being developed into clinical tests. However, several seminal studies have recently reported that DNA methylation 5mC can be de-methylated by the TET proteins resulting in 5-hydroxylmethylation 5hmC, which plays functional roles distinct from 5mC but yet is indistinguishable from 5mC by a majority of existing methylation assays. Developing enabling assays that measure 5mC and 5hmC specifically might significantly improve the performance ofmethylation biomarkers. We have shown that MeDIP-seq and 5hmC-seq as optimal approaches to globally detect 5mC and 5hmC, respectively. We have then performed genome-wide mapping of 5mC and 5hmC in 33 samples, including 11 primary benign prostate tissues, 11 localized prostate cancer tissues, and 6 castration-resistant prostate cancer tissues. Bioinformatics analysis revealed a molecular crosstalk among TET1, FOXA1-mediated enhancers, and AR signaling and identified cancer-specific methylation biomarkers which will be further validated in larger sample sets.
- Medicine and Medical Research