This week we profile a recent publication in the British Journal of Cancer from
Dr. Davide Pellacani (pictured), a Postdoctoral Fellow at the Terry Fox Laboratory.
Can you provide a brief overview of your lab’s current research focus?
I am currently a senior postdoc in Dr. Connie Eaves’s lab at the Terry Fox Laboratory / BC Cancer Agency in Vancouver, Canada. The general focus of the lab is on hematopoietic and mammary stem cells, leukaemia and breast cancer. Currently, I am studying the epigenetic regulation of human mammary cells and their deregulation in the initial steps of breast tumorigenesis. I study these processes in primary cells derived from human mammary tissue samples, which can be cultured, modified and assayed clonally in vitro and in vivo. However, the study published in the British Journal of Cancer started during my previous postdoc in Prof. Norman Maitland’s lab at the University of York, UK. There, I was interested in characterizing the DNA methylation signatures of distinct cell populations present in prostate cancer samples. I then continued these studies as a side project in Vancouver with the support of Dr. Eaves, to whom I am extremely grateful.
What is the significance of the findings in this publication?
Prostate cancer is characterized by many DNA methylation changes compared to normal tissue, however, the identification of those changes linked to the acquisition of malignant proprieties is complicated by the predominance of cells with luminal features in prostate cancers.
In this study, we measured the DNA methylation patterns of two distinct cell populations found within prostate cancer samples (called basal and luminal) and their normal counterparts. From these datasets it clearly emerged that many of the common DNA methylation alterations 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 then 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 alterations present in both luminal and basal cancer cells. We 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.
What are the next steps for this research?
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.
This research was funded by:
This work was supported by The Freemasons’ Grand Charity, Yorkshire Cancer Research program grant Y257PA , and British Columbia Cancer Agency (Strategic Priorities Fund).