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Rodent of the Week: Predicting which prostate cancers will spread

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Prostate cancers grow slowly in many men but aggressively in others. New research suggests that a group of four molecular markers found in some tumors can be used to predict whether the cancer will spread.

Published Wednesday in the journal Nature, researchers analyzed prostate cancer tissue from hundreds of men and found a four-gene signature in some tumors was linked to a more aggressive growth of the cancer.

Researchers first analyzed the Pten gene because men whose cancers lack a working copy of this gene are known to have tumors that don’t spread. They then looked at other collections of genes that may also affect tumor growth. In a study with mice whose prostate tumors lacked the Pten gene and another gene, called Smad4, the mice grew fast, large tumors. Ultimately, the researchers identified two other genes that are working partners of Smad4 and are also linked to aggressive prostate cancers in the mice.

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The four-gene signature, Pten and the three other genes, was tested in tissue samples of men who had prostate cancer and was found to more accurate than the conventional approach of predicting the likelihood of further growth.

Right now, the potential for prostate cancer to spread is measured by analyzing the cells’ appearance under a microscope. The accuracy of this test is about 60% to 70%. The four-gene marker used alone, however, was accurate about 83% of the time. Combining the two tests could improve accuracy to about 90%, the researchers said.

“It’s widely recognized that many prostate cancer patients are treated unnecessarily,” the lead author, Dr. Ronald DePinho, of Dana-Farber and Brigham and Women’s Hospital, said in a news release. “The vast majority of prostate cancers would not become life-threatening, even if left untreated. But because we can’t accurately forecast which are likely to spread and which aren’t, there is a tendency to unnecessarily subject many men to draconian interventions.”

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