Phenotype-independent DNA methylation changes in prostate cancer

Pellacani, Davide; Droop, Alastair P.; Frame, Fiona M.; Simms, Matthew S.; Mann, Vincent M.; Collins, Anne T.; Eaves, Connie J.; Maitland, Norman J.

Abstract

Background
Human prostate cancers display numerous DNA methylation changes compared to normal tissue samples. However, definitive identification of features related to the cells’ malignant status has been compromised by the predominance of cells with luminal features in prostate cancers.

Methods
We generated genome-wide DNA methylation profiles of cell subpopulations with basal or luminal features isolated from matched prostate cancer and normal tissue samples.

Results
Many frequent DNA methylation changes previously attributed to prostate cancers are here identified as differences between luminal and basal cells in both normal and cancer samples. We also identified changes unique to each of the two cancer subpopulations. Those specific to cancer luminal cells were associated with regulation of metabolic processes, cell proliferation and epithelial development. Within the prostate cancer TCGA dataset, these changes were able to distinguish not only cancers from normal samples, but also organ-confined cancers from those with extraprostatic extensions. Using changes present in both basal and luminal cancer cells, we derived a new 17-CpG prostate cancer signature with high predictive power in the TCGA dataset.

Conclusions
This study demonstrates the importance of comparing phenotypically matched prostate cell populations from normal and cancer tissues to unmask biologically and clinically relevant DNA methylation changes.

Citation

Pellacani, D., Droop, A. P., Frame, F. M., Simms, M. S., Mann, V. M., Collins, A. T., Eaves, C. J., & Maitland, N. J. (2018). Phenotype-independent DNA methylation changes in prostate cancer. The British Journal of Cancer, 119(9), 1133-1143. https://doi.org/10.1038/s41416-018-0236-1

• Journal Article Type: Article
• Acceptance Date: Jul 27, 2018
• Online Publication Date: Oct 15, 2018
• Publication Date: 2018-10
• Deposit Date: Jun 20, 2019
• Journal: British Journal of Cancer
• Print ISSN: 0007-0920
• Electronic ISSN: 1532-1827
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 119
• Issue: 9
• Pages: 1133-1143
• DOI: https://doi.org/10.1038/s41416-018-0236-1
• Keywords: DNA methylation; Prostate cancer
• Public URL: https://hull-repository.worktribe.com/output/2020204
• Publisher URL: https://www.nature.com/articles/s41416-018-0236-1
• Related Public URLs: http://eprints.whiterose.ac.uk/133612/
• Additional Information: I don't know if it is open access