Prostate cancer tied to genes

Study finds fusion of DNA material in solid tumors


Scientists have discovered a fused gene that might be responsible for a large percentage of prostate cancers, sparking hope for better diagnostic tests and, ultimately, targeted treatments for one of the most common forms of cancer in men.

The researchers say a similar genetic process might govern the development of other so-called solid tumor cancers, the most prevalent type. Scientists in Baltimore are working to replicate the results, while the study's authors are trying to develop diagnostic tests based on the findings.

Scientists already knew that a cell can turn cancerous when two gene fragments - one healthy and one that causes cancer - combine into one "fused" gene.

Similar genes are associated with cancers such as leukemia, lymphoma and soft tissue sarcomas. But the findings published in today's issue of the journal Science mark the first time such a rearranged gene has been implicated in a cancer characterized by solid tumors.

"Our study speculates equivalent rearrangements exist for colon cancer, breast cancer" and others, said Dr. Arul M. Chinnaiyan, the University of Michigan Medical School pathologist who directed the study.

The prostate is a small gland at the base of the urethra that frequently becomes enlarged in middle age. It is the second most common location for cancer in men, behind skin cancer.

Dr. Nancy Dawson, a prostate cancer specialist who supervises clinical trials at the University of Maryland Medical Center, said the finding is significant even if it applies only to that disease - which is expected to be diagnosed in more than 232,000 men this year and kill more than 30,000, according to the American Cancer Society.

But, she said, "This may be bigger than prostate cancer."

In Michigan, Chinnaiyan's lab is working on a urine test for prostate cancer based on the findings.

Doctors there hope it will be more definitive than the current test for prostate specific antigen, or PSA. That test can be confusing because it looks for elevated levels of an antigen that's present in both healthy men and those with enlarged or cancerous prostates.

Some men with relatively low PSA scores wind up having cancer; many with relatively high scores don't.

Scientists also hope the discovery will lead to a drug that blocks the action of the fused gene. If successful, it could be similar to Gleevec, which interferes with the workings of a fused gene that causes chronic myelogenous leukemia.

If it turns out that gene fusions cause or hasten the development of other solid tumor cancers, scientists could try to develop specific drugs to treat them.

Although researchers were excited by the findings, Sudhir Srivastava of the National Cancer Institutes joined colleagues in urging caution. They noted that many promising discoveries ultimately fail with a disease that frustrates physicians by constantly mutating.

Although scientists might be able to develop a new diagnostic test for prostate cancer virtually overnight, validating any test to ensure reliability takes much longer, and drugs take years to bring to market.

"This is the first study," said Srivastava, director of the National Cancer Institute's Early Detection Research Network, of which the University of Michigan researchers are a part. "It needs to be replicated."

Even so, Srivastava said, the findings are already having an impact. Some prostate experts have reworked lab "to-do" lists, scratching off planned projects to see whether they can repeat the Michigan results.

Dr. William Isaacs, a Johns Hopkins University expert on prostate cancer heredity, is one of them. His own work years ago located a prostate gene passed from mothers to sons. Now he's wondering whether the fused gene discovered by the Michigan team might help predict how aggressive - and potentially lethal - a particular prostate cancer will be.

"We are actively working to see if we can confirm these data," Isaacs said. "We are very interested in this question of what makes a bad prostate cancer or a good prostate cancer, in terms of outcome."

At the University of Maryland, Dawson told colleagues about the research on rounds this week, shortly after hearing the news. She also began thinking about questions that researchers might eventually answer using tissue samples from patients in clinical trials.

"Now, you're going to go looking at this in various stages of prostate cancer: Is it mostly seen at the end? Mostly seen at the beginning?" she asked. "Does finding this predict that you're more likely to respond to certain therapies that we already have available?"

The abnormal gene Chinnaiyan's lab found appears when one of two genes (known as ERG or ETV1) attaches to another gene specific to prostate cancer. Both ERG and ETV1 belong to a family of genes already associated with a bone cancer known as Ewing's sarcoma, and other malignancies.

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