MedicalResearch.com Interview with:
Davide Pellacani Ph.D.
Postdoctoral Fellow, Eaves’ Lab
Terry Fox Laboratory,
BC Cancer Research Centre
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Prostate cancer is characterized by frequent DNA methylation changes compared to normal tissue. Nevertheless, understanding which of those changes lead to the acquisition of malignant proprieties is complicated by the predominance of cells with luminal features in prostate cancers.
In this study we generated DNA methylation maps of two distinct cell populations found within prostate cancer samples (called basal and luminal) and their normal counterparts. These datasets clearly showed that many of the common DNA methylation changes found in prostate cancer are present in luminal cells from both cancer and normal tissues. These changes are not necessarily cancer-specific, and are likely due to the bias associated with analyzing tissues in bulk, where most cancer cells have luminal-like features.
We used these datasets to derive two cancer-specific and phenotype-independent DNA methylation signatures: one specific to prostate cancer luminal cells, and one composed of changes measured in both luminal and basal cancer cells.
We then validated the potential clinical utility of these signatures by testing their ability to distinguish prostate cancer from normal samples, and tumours that have already escaped the prostate from those that have not, using the publicly available dataset from The Cancer Genome Atlas.
MedicalResearch.com: What should readers take away from your report?
Response: This study shows the importance of using phenotypically matched cell populations from normal and cancer tissues to reveal biologically and clinically relevant epigenetic changes in prostate cancer.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: This first study confirmed that dissecting prostate cancer into its major phenotypic components is a successful strategy to better understand its epigenetic alterations. Understanding which of these cancer-specific alterations are important in conferring malignant proprieties to prostate cells will be an obvious next step.
Moreover, we are interested in further validating whether the DNA methylation signatures obtained are applicable in a clinical scenario, by developing sensitive assays to be utilized with blood and urine samples.
Davide Pellacani, Alastair P. Droop, Fiona M. Frame, Matthew S. Simms, Vincent M. Mann, Anne T. Collins, Connie J. Eaves, Norman J. Maitland. Phenotype-independent DNA methylation changes in prostate cancer. British Journal of Cancer, 2018; DOI: 10.1038/s41416-018-0236-1
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