Scientists at the Johns Hopkins Kimmel Cancer Center found in a genome-wide analysis of 13 men with metastatic prostate cancer that there were consistent epigenetic “signatures” or “marks” across all metastatic tumors in each of the subject men. The discovery contradicts the current belief that epigenetic marks that sit on the nuclear DNA of cancer cells and alter gene expression vary so much within each individual’s cancer that they have little or no value as targets for therapy or as biomarkers for treatment response and predicting disease severity.
Published in the journal Science Translational Medicine, the study describes the genomic analysis of 13 men who died of advanced prostate cancer and whose tissue samples were collected after a rapid autopsy. The researchers sampled from three to six metastatic sites in each of the men and one to three samples of their normal tissue were also analyzed.
“Knowing both the genetic and epigenetic changes that happen in lethal prostate cancers can eventually help us identify the most aggressive cancers earlier and develop new therapies that target those changes,” says Srinivasan Yegnasubramanian, M.D., Ph.D., assistant professor of oncology at The Johns Hopkins University School of Medicine. “But there has been an open question of whether epigenetic changes are consistently maintained across all metastatic sites of an individual’s cancer.”
The research team found that while methylation patterns vary from one patient to another, many methylation patterns occur “very consistently” within different metastatic sites in an individual patient. They identified more than 1,000 regions of the genome where various types of DNA methylation were consistently maintained within their 13 subjects’ genomes.
According to Dr. Yegnasubramanian, “As they evolve and grow, cancer cells acquire and maintain changes that enable them to continue thriving…… We know that cancer cells maintain and pass along genetic changes in the nucleus of cells across metastatic sites, and our research now shows that epigenetic changes also are maintained to nearly the same degree.”
Yegnasubramanian also said, “Our study shows that for prostate cancer, at least, each person develops his own path to cancer and metastasis, and we can find a signature of that path in the epigenetic marks within their tumors.” He also believes that certain of these epigenetic changes can be grouped into clusters to be used as biomarkers signaling the presence of a lethal cancer or even as treatment targets.
A better understanding of the genetic and the epigenetic structure of advanced prostate cancer will lead us to new bio-markers and treatment options for men with advanced prostate cancer. I am hoping that future research will also evaluate the genetic structure of prostate cancer still in the gland to allow us to make better decisions on what specific cancers need treatment and which can be simply monitored.
Joel T. Nowak, M.A., M.S.W.