The role of enhancer elements in prostate cancer

Prostate cancer (PCa) is one of the most common and heterogeneous cancers in men. The clinical course of PCa is highly variable and requires reliable prognostic markers for individualized approaches in therapy (Gerhauser et al., 2018).

We postulate that DNA methylation differences in tumor samples from PCa patients with good and bad prognosis can be used to predict the course of the disease. We have acquired genome-wide methylation data for prostate cancer samples and FACS-sorted prostate (cancer) cell fractions at single CpG resolution by sequencing bisulfite-converted DNA. These data allow us to identify truly prostate cancer-specific methylation differences from normal basal and luminal epithelial cells, which represent the cell types-of-origin of prostate cancer.

Correlation with gene expression data and bioinformatic classification models will allow the prioritization of differentially methylated regions as biomarkers with prognostic relevance, which we will validate in the ICGC cohort of early onset prostate cancer.

Since cell type- and cancer-specific methylation differences occur mainly in enhancer regions that have been insufficiently covered in previous studies, we expect a significant breakthrough in the understanding the etiology and the driving events in prostate carcinogenesis in addition to the development of highly specific and selective prognostic biomarkers for the clinics.

In future studies, these markers can be validated in relatively noninvasive biospecimen such as plasma or urine samples.

• funded by Baden-Württemberg (BW) Foundation, Program Epigenetics

Reference

Clarissa Gerhauser, Francesco Favero, Thomas Risch, ..., Jan O. Korbel, Thorsten Schlomm, Joachim Weischenfeldt, Molecular evolution of early onset prostate cancer identifies molecular risk markers and clinical trajectories. Cancer Cell 34, 996-1011 (2018) doi: 10.1016/j.ccell.2018.10.016.