Johns Hopkins researchers are now pointing to a set of genetic defects in a single cell that are different for each person's prostate cancer.
Researchers have tracked how cancer process began in 33 men with prostate cancer, who died of the disease. "These were not your average autopsies. We dissected every bit of tumor, in the primary and metastatic sites, and recorded exactly where each piece of tissue came from, analyzed it, and databased the findings," Nature magazine quoted pathologist Dr. G. Steven Bova, assistant professor of pathology at Johns Hopkins, as saying.
AdvertisementDuring the study, he and his colleagues examined 150,000 slides and 30,000 blocks of tissue.
The researchers, who took 14 years to complete this study, have revealed that part of the challenge was in finding men living with prostate cancer who would agree to have their body autopsied immediately after they died.
"Many of the men were motivated to join the study in hopes of leaving some legacy that might lead to cures for this cancer," says Bova, who holds secondary appointments in the departments of pathology, genetic medicine, health sciences informatics, oncology, and urology at Johns Hopkins.
"Much is unclear and appears chaotic about how cancer spreads, but analyzing genetic markers allows us to trace its roots backward, somewhat like ancestry," adds Bova.
The researchers scanned genes spanning the whole genome in the autopsy samples looking for areas of copy number variation. They did so by attaching the DNA to special silicon chips, and then photographed them with a computer program that produces a report with varying colors representing the amount of DNA in the sample.
Upon comparing the patterns of gains and losses in tissue samples from multiple metastatic sites in 29 of the men, the researchers identified unique copy number changes, as well as ones that were shared between multiple metastatic sites in each man and with other men in the study.
In several men, the investigators found cells in different areas of metastasis that contained missing chunks of DNA in one common region of the genome.
While the exact location of the DNA loss was different for each man, all occurred in the same DNA region.
"Each person has a different set of defects that contributes to the cancer," says Bova.
Metastatic sites develop from cancer cells that break off of the primary cancer. If cancer cells at more than one metastatic site carry a common set of nonrandom genetic defects, it is likely that these cells are derived from a single parent cell, says Bova.
When the researchers studied tissue samples from 14 of the 33 men at the highest available resolution, all showed common genetic patterns across metastatic sites, suggesting a single cell source for their cancer.
Bova says that future studies will help determine whether the common set of changes shared by the various metastatic sites arose in a single "big bang" in the prostate or if the changes accumulated more slowly over time.
According to him, such autopsy studies of metastatic cancer can provide a molecular catalog of cellular defects specific to individuals and general groups, and help narrow the focus of research and guide personalized cancer therapy.
A research article on the study has been published in the journal Nature Medicine.