The Genome is the Destination, Epigenetics is the Route Map
Researchers at the Johns Hopkins Kimmel Cancer Center, looking into prostate cancer, have discovered some common epigenetic characteristics. Their analysis was across the entire genome in thirteen metastatic prostate cancers. In all of the metastatic tumors in every one of the patients, there are some common ‘markers’ that may be the best hope of better diagnosis and treatment for this difficult form of cancer.
The epigenetic signatures reside on the nuclear DNA of mutated cancer cells and significantly change the gene development. Current medical thinking is that there is so little commonality among tumors and individual patient’s cancers that there is little chance of using them as pre-indicators for therapy, or as ‘biomarkers’ for more individuated treatment, or even as accurate predictors of cancer aggressiveness.
The latest discoveries can be read in this month’s issue of Science Translational Medicine. It details the genomic analysis of 13 men who suffered from fatal metastatic prostate cancer. Their DNA was taken from tissue biopsies taken during early autopsies. Each of the metastatic areas in every one of the patients was sampled. So there were between 3 and 6 samples for each.
In addition up to three examples of healthy non-cancerous tissue were tested for comparison purposes and to pin down exactly the molecular marks consisting of methyl clusters that link to areas of the genome. This process called ‘DNA methylation’. This process is just one within a growing area of scientific research into epigenetics. It is a process that understood to be both catalyst and regulator of gene activation.
Mutations in these epigenetic processes are also thought to be the source of cancers. Research aims to help us understand both the gene development and the epigenetic occurrences within deadly prostate cancers. It may ultimately allow us pick out the most aggressive forms of tumor sooner and thereby develop treatments aimed specifically at those changes. At least this is the belief of the Johns Hopkins team.
It is the big question in this field of epigenetics, whether the changes are consistent in all cancer areas in every patient. This small study provides a partial insight. They discovered that while methylation patterns were different in different people, many of them were ‘regulars’ in the metastatic areas within individuals. They could point in total to over a thousand variations on DNA methylation that cropped up consistently in their 13 patient’s genomes. It is clear that tumors take what they need to develop in these epigenetic processes.
It is already clear that cancers retain and pass on genetic alterations within cell nuclei and across metastatic sites and now it is clear that epigenetic changes do likewise, almost but not quite to the same degree.
This study is limited to just prostate cancer. It indicates that individuals develop their own routes to cancer and metastasis, and it is possible to identify the epigenetic flags within their cancers. If we can then gather epigenetic changes into identifiable clusters they may be telltale predictors of the fatal cancers and perhaps even more importantly they can identify the non-lethal ones.