Prostate cancer is the most commonly diagnosed malignancy among males within developed countries. Most often the majority of prostate cancer is thought of as an organ-confined disease with little genetic variation. However, data in recent years is beginning to bring into focus that many prostate tumors display substantial amounts of genetic heterogeneity, leading to differential mortality rates.
Now, prostate cancer researchers in Canada have sketched a molecular portrait providing a complete picture of what they describe as a localized, multi-focal disease within the prostate gland, as well as identifying a new gene subgroup acting as a molecular driver for tumor progression.
“Our research shows how prostate cancers can vary from one man to another—despite the same pathology under the microscope—as well as how it can vary within one man who may have multiple tumor types in his prostate,” explained Robert Bristow, M.D., Ph.D., clinician-scientist at Princess Margaret Cancer Centre, Toronto and senior author on the study. “These sub-types may be important to determining the response to surgery or radiotherapy between patients.”
The findings from this study were published recently in Nature Genetics through an article entitled “Spatial genomic heterogeneity within localized, multifocal prostate cancer.”
Specifically, the study involved the molecular profiling of 74 patients with relatively high aggressiveness scores. From this group, whole genome sequencing was performed on samples from five patients whose prostates were surgically removed. The investigators carefully analyzed the genetic backgrounds of each tumor sample, assigning individual aggression scores to the discreet cancer foci regions they identified. The data revealed that even small cancers within the prostate can contain very aggressive cells capable of varying long term disease prognosis.
Additionally, Dr. Bristow and his colleagues identified two members of the MYC oncogene family that played essential roles in tumor development. The researchers identified C-MYC as being the driver of aggressiveness for the disease and L-MYC, which has already been implicated in lung cancer development, playing a critical role in tumor progression.
“This discovery of a new prostate cancer-causing gene gives researchers a new avenue to explore the biology of the disease and improve treatment,” stated Paul Boutros, Ph.D., principal investigator at the Ontario Institute for Cancer Research and lead author on the current study. “By showing that mutations in prostate cancer vary spatially in different regions of a tumor, this study will aid in the development of new diagnostic tests that will improve treatment by allowing it to be further personalized.”
Interestingly, the researchers determined that half of all prostate patients have either C-MYC or LMYC mutations, but never both. Dr. Bristow thinks that this study takes an important step forward in identifying new biomarkers for prostate cancer and developing novel treatment options for patients.
“Our findings suggest we are getting closer to subtyping prostate cancer based on which gene is present to determine a patients' disease aggression in terms of the risk of spread outside the prostate gland at time of treatment,” said Dr. Bristow. “In developing this research tool into a clinical test within three years, we hope to inform doctors and patients about specialized treatments for each prostate cancer patient.”