Epigenetic Analysis of Circulating Tumor Cells
Abstract
Despite advances in the field, metastatic prostate cancer prognosis remains poor. Although genomic biomarkers are being assessed for clinical relevance, epigenetic modifications have been found to be much more common, some found in more than 90% of prostate cancer tumors. Two of these modifications are GSTP1 and PRAC DNA hypermethylation. Circulating tumor cells (CTCs) provide a minimally invasive way to monitor patient disease, however they are a rare cell population and current methods of epigenetic analysis are not sensitive enough to assay DNA methylation from such a population. We have developed an assay that can sensitively and specifically enrich for methylated DNA from rare cell populations and have optimized this assay using cell line models to enrich for methylated GSTP1 from as little as one cell. We have tested this assay in patient biopsies, either flow sorted by tumor compartment or unsorted populations, and found GSTP1 methylation in 100% of patient tissue tested, but not in white blood cells. We also chose 7 patients with castration resistance prostate cancer (CRPC) as a pilot study for GSTP1 methylation analysis in CTCs. 5 out of 7 (71%) CRPC CTC samples had GSTP1 methylation detectable above background.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2018
- Accession Number
- AD1060239
Entities
People
- Tamara Rodems
Organizations
- University of Wisconsin System