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A Novel Approach to Assay DNA Methylation in Prostate Cancer

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Technical Report,30 Sep 2014,29 Sep 2015

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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 of methylation biomarkers. During this reporting period, we have performed genome-wide mapping of 5mC and 5hmC in 33 samples, including 11 primary benign prostate tissue, 11 localized prostate cancer tissue and 6 castration-resistant prostate cancer tissue. We are working on to establish a bioinformatics system to handle and analyze the large amount of sequencing data. Further, in an effort to establish a system to manipulate DNA methylation, we found that FOXA1, a pioneer factor of androgen receptor, directly induces TET1 expression and interacts with TET1 protein, leading to lineage-specific enhancer activation. Several manuscripts have been either published or under submission.

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