Investigator: Tarek Bismar, MD – Associate Professor, University of Calgary
Combined role of TMPRSS2-ERG gene fusion and PTEN genomic deletions in prostate cancer progression
The two most common genomic aberrations in prostate cancer are the ERG gene rearrangements and PTEN deletion. TMPRSS2-ERG represents the most common form of ERG rearrangements. It is an aberration in the genome of prostate cancer cells created when two distinct genes, TMPRSS2 and ERG (found in two different regions of DNA), are shuffled around and erroneously juxtaposed. PTEN is a tumor suppressor gene (a gene that protects against cancer) and is often deleted from the DNA code of prostate cancer cells. Dr. Bismar’s work centers on identifying the molecular differences between prostate cancer cells that harbor these genetic alterations and prostate cancer cells that do not.
A recent report by Dr. Bismar and colleagues showed that in localized prostate cancer the presence of both TMPRSS2-ERG and PTEN deletion were significantly associated with high-grade prostate cancer. This indicates that these genetic alterations may cause a more aggressive prostate cancer. In the same report they demonstrate that these genetic alterations are early events in prostate cancer development, which is in agreement with other published studies.
To understand how TMPRSS2-ERG and PTEN deletion change the behavior of prostate cancer cells, Dr. Bismar compared the molecular profile of tissue samples from patients who were either positive or negative for the two genetic alterations. In his comparative analysis he has identified a list of genes that are either elevated or depleted in prostate cancers with in relation to their TMPRSS2-ERG and PTEN status. So far, Dr. Bismar has discovered 5 novel, candidate prostate cancer biomarkers (a molecule that indicates a biological process or pathogenesis) that are discriminate benign tissue, from localized prostate cancer and lethal prostate cancer. Some of these genes may also represent new therapeutic targets for patients with prostate cancer. Dr. Bismar and his team are currently working on validating their findings in larger studies.