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Researchers Have Identified Gene Fusions That Trigger Prostate Cancer

by VR Sreeraman on Aug 2 2007 4:52 PM

In a new study, US researchers have found that special gene fusions help trigger prostate cancer.

Researchers at the University of Michigan (U-M) Comprehensive Cancer Center found that pieces of two chromosomes can trade places with each other and cause two genes to fuse together.

These fused genes then supersede the "off" switch that prevents uncontrolled cell growth -- key to the development of prostate cancer.

The researchers, who conducted experiments with mice and cell cultures, found that this prostate-cancer causing fusion can take place in a number of genes from the same family. The genes from that family fuse with eitherERGorETV1, two genes known to be involved in several types of cancer.

"Each of these switches, or gene fusions, represent different molecular subtypes. This tells us there's not just one type of prostate cancer. It's a more complex disease and potentially needs to be treated differently in each patient," Nature quoted lead author Dr. Arul Chinnaiyan, director of U-M's Michigan Center for Transitional Pathology, as saying in a prepared statement.

Several abnormal gene fusions were involved in 60 percent to 70 percent of the prostate cancer cell lines examined by the researchers. The genes involved in the fusions are controlled by different mechanisms, including four genes regulated by the male sex hormone androgen, which is known to fuel prostate cancer.

Identifying the gene fusion that caused a patient's prostate cancer could help doctors determine the best treatment. For example, if an androgen-regulated gene is involved, androgen therapy may be appropriate, the research team said.

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"Typing someone's prostate cancer by gene fusion can affect the treatment given. We would not want to give androgen to someone whose prostate cancer gene fusion is not regulated by androgen," says Chinnaiyan, who is the S.P. Hicks Collegiate Professor of Pathology at the U-M Medical School.

Rearrangements in chromosomes and fused genes are play a significant role in blood cell cancers like leukemia and lymphoma, and in Ewing's sarcoma. A fused gene combination that plays a role in chronic myelogenous leukemia led researchers to build up the drug Gleevec, which has dramatically improved survival rates for that disease.

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Chinnaiyan believes that the prostate gene fusions will ultimately lead to parallel treatments for prostate cancer.

"More immediately, we hope to develop tests for diagnosis or prognosis. But long-term, we hope this will lead to better therapies to treat prostate cancer. The key challenge is to find a drug that would go after this gene fusion," Chinnaiyan says.

The study appears in the Aug. 2 issue of the journal Nature.

Source-ANI
SRM/C


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