Genetic Footprints Show Promise in Personalized Management of Advanced Cancer

What is methylation? It's a word that has been popping up for several years now in discussions of prostate cancer. In basic terms, it means that a gene's physical shape changes – think of a LEGO with an extra nub that doesn't fit where it used to, or a lock that no longer works with its key. When this happens to a gene, this is what scientists call an "epigenetic" change; as its shape changes, so does its ability to function. Genes that are supposed to protect the body against enemy invaders are suddenly silenced, for example, and don't put up a defense against cancer. 

But these changes, called epigenetic marks, are also like tiny footprints, and as such, they can be very useful for scientists who know how to look for them: Track the methylation, and you'll find the cancer cells, too; currently, biomarkers to detect methylated genes in biopsied prostate tissue and even urine specimens are being developed. Understanding and being able to pinpoint methylated genes may also become a diagnostic tool to help physicians predict the aggressiveness of a man's cancer. Also, scientists believe, this presents a promising new potential target of therapy – a way to get at cancer that has spread beyond the prostate. 

As part of an interdisciplinary team, cancer researcher Vasan Yegnasubramanian, M.D., Ph.D., and colleagues in his lab have mapped out DNA methylation on a genome-wide scale in the worst, most aggressive forms of prostate cancer. "For this research, we used multiple lethal metastatic prostate cancers from each of several men who died of their prostate cancer," Yegnasubramanian says. "Our analysis has revealed that although the epigenetic alterations in lethal metastatic prostate cancer are highly diverse across individuals, they are strikingly maintained across all of the metastases within each individual." Yegnasubramanian believes that this work has exciting implications: "This discovery highlights the importance and promise of personalized medicine strategies for management of advanced prostate cancer," he says. "Our research team plans to exploit this new understanding of the epigenetic architecture of the lethal metastatic prostate cancer genome to develop new biomarkers for prostate cancer risk stratification and new therapies targeting these epigenetic alterations as part of a personalized medicine approach. This work was supported in part by the Patrick C. Walsh Research Fund.

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