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The Patrick C. Walsh Prostate Cancer Research Fund

A Better Way to Detect Epigenetic Changes

There are genetic changes in cancer — changes in the DNA sequence of genes that spark unbridled cell growth and replication and lead to cancer — and then there are “epigenetic” changes. These are changes that can turn off or turn on a gene without changing the DNA sequence. This can happen in cancer cells and also in pr ecancerous cells; currently, these changes are not very easy to detect and monitor. “Most of the ways we can determine the presence of epigenetic changes involve averaging signals from assays that are designed to look for changes in man y cancer cells,” says Angelo M. De Marzo, M.D., Ph.D., Professor of Pathology, Oncology, and Urology. “However, these techniques can’t determine, at the single cell level, precisely which changes are occurring in which cell types . This limits our understanding of how cancers arise and progress.”


For example, some epigenetic changes involve subtle changes of DNA methylation — basically, these changes are akin to fiddling with the tumblers on a lock. “DNA methylation alterations in prostate cancer have been shown to have extremely high sensitivity and specificity for distinguishing prostate cancer tissues from normal tissues,” but to spot them, scientists must extract DNA from cells and then subject it to various solution-based assays, a process that is time-consuming and expensive. A great deal of the work showing extensive, prostate cancer-specific DNA methylation alterations has been conducted by Srinivasan Yegnasubramanian, M.D., Ph.D., Associate Professor of Oncology. Yegnasubramanian first started on DNA methylation studies in prostate cancer when he worked in the laboratory of William G. Nelson, M.D., Ph.D., as a graduate student, and he has continued this work as an independent investigator. Wouldn’t it be nice if scientis ts could measure these changes right in the specimens of prostate tissue? De Marzo and a team of investigators, who have worked together on DNA methylation changes in prostate cancer for more than a decade, are determined to overcome this roadblock. The the fact that there isn’t a good way to do this kind of “in situ” testing, they realized, has prevented pathologists from routinely checking for methylation changes to help diagnose prostate cancer, and it’s prevented scientists from using it to study prostate cancer. “Clearly, the development of next-generation technologies for in situ detection of epigenetic changes would be of immense value in improving our understanding and clinical management of prostate and other cancers.”


Wouldn’t it be nice if scientists could measure these subtle changes right in the prostate tissue?


With support from the Patrick C. Walsh Prostate Cancer Research Fund, De Marzo, the Virginia and Warren Schwerin Scholar, Yegnasubramanian, Nelson and post docs Michael Haffner, M.D. Ph.D., and Ibrahim Kulac, M.D., are working to develop such highly innovative technologies to enable the detection of epigenetic changes in situ, “with a high degree of sensitivity down to single-molecule detection.”

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