To spread or not to spread?
Thousands of men each year could be spared the inconvenience, discomfort, and potential risk of treatment for prostate cancer if there were a simple test for determining whether their cancer is likely to stay harmlessly within the prostate gland or spread beyond it to bones and other tissues, potentially becoming fatal. To devise such a test, researchers would need access to prostate cancer tissue both from men who received treatment and those who did not. The samples could then be analyzed to see if the lethal and non-lethal varieties have different genetic "signatures." But the American tendency to treat the vast majority of prostate cancers, rather than take a chance that some of them won't be aggressive, limits the amount of tissue available for comparison.
The situation is quite different in Sweden, where "watchful waiting" is a more common practice. Over the past two decades, Swedish scientists have collected thousands of prostate cancer samples, along with detailed follow-up data on each patient's course of disease.
In a meeting of population science and molecular-age technology, Dana-Farber and Swedish scientists have joined in an effort to analyze the specimens for genetic variations that signal a likelihood to spread or stay put. The partnership originated a decade ago when Kantoff met a Swedish researcher at a conference and discussed possible collaborative work, but it gained momentum in 2004, when DFCI and Swedish investigators held a "summit" to launch the project. The decisive factor was new technology that makes it possible to measure the actions of single genes or thousands of genes at once.
There was a technical hitch, however, that could have stopped the plans in their tracks. When the Swedish tissue-collection effort began, tumor samples were preserved in a substance called formalin, rather than being frozen, as they would be today. Formalin-encased tissue cannot be "read" by the screening equipment normally used to record genes' activity levels.
At Dana-Farber, Todd Golub, MD, and pathologist Mark Rubin, MD, of Brigham and Women's Hospital devised a way of using existing DNA-sequencing technology to map gene-activity patterns in the tissue from Sweden. "Putting this technology to a new use was not only helpful in this research project, but it may have broader applications as well," says Golub. "It may eventually allow doctors to conduct molecular genetic tests in smaller community hospitals and medical practices, where tissue samples can be more easily stored in formalin than frozen."
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