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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.

Authors

Davide Pellacani

Alastair P. Droop

Matthew S. Simms

Vincent M. Mann

Anne T. Collins

Connie J. Eaves

Norman J. Maitland

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.

Journal Article Type Article
Publication Date 2018-10
Journal British Journal of Cancer
Print ISSN 0007-0920
Electronic ISSN 1532-1827
Publisher Cancer Research UK
Peer Reviewed Peer Reviewed
Volume 119
Issue 9
Pages 1133-1143
Institution Citation Pellacani, D., Droop, A. P., Frame, F. M., Simms, M. S., Mann, V. M., Collins, A. T., …Maitland, N. J. (2018). Phenotype-independent DNA methylation changes in prostate cancer. The British journal of cancer / Cancer Research Campaign, 119(9), 1133-1143. https://doi.org/10.1038/s41416-018-0236-1
DOI https://doi.org/10.1038/s41416-018-0236-1
Keywords DNA methylation; Prostate cancer
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