Researchers find 'on switches' that cause prostate cancer
Researchers at the Comprehensive Cancer Center have discovered how genes turn on the switch that leads to prostate cancer.
The team discovered that pieces of two chromosomes can trade places with each other and cause two genes to fuse together. The fused genes then override the "off" switch that keeps cells from growing uncontrollably, causing prostate cancer to develop.
By testing these gene fusions in mice and in cell cultures, the researchers showed that the fusions are what cause prostate cancer to develop.
But it's not just one set of genes that fuse.
The researchers found that any one of several in a family of genes can become scrambled and fuse. Results of the study appear in the Aug. 2 issue of Nature.
"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," says lead study author Dr. Arul Chinnaiyan, director of the Michigan Center for Translational Pathology, a new U-M center whose goal is to translate research into real world practice.
The gene fusion research is the centerpiece project of the new center.
Chinnaiyan, who is the S.P. Hicks Collegiate Professor of Pathology at the Medical School, believes the prostate gene fusions eventually will lead to similar 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.
About 218,890 men will be diagnosed with prostate cancer this year, and 27,050 will die from the disease, according to the American Cancer Society.
In addition to Chinnaiyan, U-M study authors were Scott Tomlins, Saravana Dhanasekaran, Bharathi Laxman, Qi Cao, Beth Helgeson, Xuhong Cao, Dr. David Morris, Anjana Menon, Xiaojun Jing, Bo Han, Dr. James Montie, Dr. Kenneth Pienta, Diane Roulston, Dr. Rajal Shah, Sooryanarayana Varambally and Dr. Rohit Mehra.
Dr. Mark Rubin, from Brigham and Women's Hospital, Dana-Farber Cancer Institute and Harvard Medical School, also is a study author.
Funding for the study came from the U.S. Department of Defense, the National Institutes of Health, the Early Detection Research Network, the Prostate Cancer Foundation and Gen-Probe Inc.
For information about prostate cancer and currently available treatments, go to www.mcancer.org.