Findings from a recent genomic study published in Nature provide more evidence on the migration of prostate cancer metastatic cells to different parts of the body, forming new tumor sites that can spread on their own. The findings undermine a previous assumption that cells with metastatic potential originate only from the primary cancer location.
“The idea that metastatic tumors can seed and establish other metastatic tumors in patients is different from traditional theories that the primary tumor is solely responsible for disseminating cancer cells with metastatic potential,” William Isaacs, Ph.D., Professor of Urology at the Johns Hopkins Brady Urological Institute and a member of The Johns Hopkins Kimmel Cancer Center, said in a recent news release. “The new genomic information lends more support to the idea that treatments for metastatic cancers should be a combination of therapies that target a variety of genetic pathways.”
For this study, a research team involving scientists from the Wellcome Trust Sanger Institute, University of Tampere in Finland and also researchers of the International Cancer Genome Consortium, conducted a comprehensive genomic and bioinformatics analysis of tumor tissue samples and discovered that the genetic profile of cells within metastatic prostate tumors corresponded to the profile of new tumors from other metastatic locations.
The team utilized a catalogue of the genetic profile of a total of 51 tumors collected from 10 patients with prostate cancer autopsied at Johns Hopkins Hospital, along with normal tissue samples from each of these patients.
Genomic sequencing analysis revealed that “even though a single cell begins the metastatic process, the disease becomes very heterogeneous as it spreads throughout the body over time, both between and among individuals. In individual patients, each metastatic site becomes an entity unto itself,” according to Dr. Isaacs, who also is a professor of oncology at the Johns Hopkins University School of Medicine.
The team discovered that 5 of the 10 patients had patterns of genetic mutations within many metastatic lesions. This further suggests that the lesions were originated from multiple metastatic sites. In 7 of the 10 patients, metastatic tumors were genetically more identical to each other than to the original tumor.
These new results add evidence to a previous study conducted in 2009 by G. Steven Bova, M.D., who is now a scientist at the University of Tampere in Finland. In that study, published in Nature Medicine, researchers identified similar genetic patterns across metastatic sites.
This new study used a new set of tissue samples from autopsied prostate cancer patients. “Nearly every tissue and bone in the body was biopsied, and Dr. Bova and the autopsy team collected thousands of samples from these men who generously donated their tissues to science,” said Dr. Isaacs.
Isaacs, Bova and their colleagues at Johns Hopkins initiated the autopsy program in the year of 1994, when genome sequencing did not exist and when there was limited available metastatic tissue. “These samples, along with their annotations, are even more valuable now since we can use them in very sophisticated genetic studies such as the current one,” said Dr. Isaacs. “The contributions these men made will hopefully produce more illuminating results that will pave the way for better treatment and prevention of prostate cancer.”