laboratory analysis techniques and gene sequencing to detect gene fusions between TMPRSS2 and ERG or ETV1 in prostate cancer tissue samples. "Of 22 cases with high expression of ERG or ETV1, 91 percent showed evidence of a fusion with TMPRSS2," said Scott Tomlins, a U-M graduate student in pathology and first author of the Science paper. "Our results indicate that more than half of all prostate cancer cases have one of these two fusions."
Tomlins adds that TMPRSS2 may fuse to other members of the ETS family, in addition to ERG and ETV1. "We think there are more fusions. We just haven't found them yet," he says. "To develop a diagnostic test with full sensitivity, it will be important to identify all the molecular fusions, and we are working on that now."
"We are especially excited by the profound implications these findings have for the treatment of prostate cancer," Chinnaiyan says. "It will allow us to categorize prostate tumors by molecular sub-type, which could help determine the most effective treatment for each patient."
"This collaborative effort has yielded an important molecular biomarker that will help us better detect prostate cancer and ultimately help clinicians determine the risk of dying from the disease," says Mark A. Rubin, M.D., chief of urologic pathology at Brigham and Women's Hospital, who is also an associate professor of pathology at Harvard Medical School and a co-author on the paper.
In future research, U-M scientists hope to identify small molecule inhibitors for the genes involved in prostate cancer, which would be analogous to Gleevec - a drug designed to target the BCR-ABL gene fusion that causes chronic myelogenous leukemia. The U-M research team plans additional studies to verify that gene fusion induces prostate cancer in research animals. And they will search for recurrent chromosomal rearrangements in other common epithelial cancers.
The research was supported by the National Cancer Institute's Early Detection Research Network, the National Cancer Institute's Specialized Program of Research Excellence in Prostate Cancer, the American Cancer Society, the Department of Defense, the U-M Comprehensive Cancer Center Bioinformatics Core and the U-M Medical Scientist Training Program.
The University of Michigan has filed a provisional patent application on this research technology.
Additional research collaborators from U-M include research fellows Saravana Dhanasekaran, Ph.D., Rohit Mehra, M.D., and Sooryanarayana Varambally, Ph.D.; Xuhong Cao, research associate; James Montie, M.D., the Valassis Professor of Urological Oncology; Rajal B.Shah, M.D., clinical assistant professor of pathology; and Kenneth J. Pienta, M.D., professor of internal medicine and urology. Additional collaborators from Brigham and Women's Hospital include Sven Perner, Xiao-Wei Sun, Joelle Tchinda and Charles Lee. Rainer Kuefer from the University of Ulm in Germany also collaborated in the research study.
Citation: Science: 310 (5748), October 28, 2005.
Patients seeking more information about currently available cancer treatments can call the Cancer AnswerLine at 800-865-1125 or visit www.mcancer.org.
Other social bookmarking and sharing tools:
Note: Materials may be edited for content and length. For further information, please contact the source cited above.
Note: If no author is given, the source is cited instead.