The gene, not previously known to be a tumor suppressor, most likely plays a role in regulating and maintaining normal tissue organization. The researchers have shown that the gene, known as EphB2, is inactivated in prostate cancer. This is the first time abnormalities in the gene have been linked to cancer. They believe loss of the gene's function leads to disorganization of cells and also encourages the growth and survival of prostate cancer cells.
"This finding provides critical insight into the factors that cause prostate cancer, which can be used for development of additional diagnostics and therapeutics for prostate cancer," said Dr. Spyro Mousses, head of TGen's Cancer Drug Development Laboratory and the paper's senior author. "Much additional research is warranted to determine the extent of its involvement in prostate cancer and other cancers as well."
"These findings represent a significant advancement in prostate cancer research, as the number of current treatment options for advanced prostate cancer remains limited," said Dr. John Carpten, Senior Investigator at TGen, Director of its Genetic Basis of Human Disease Division, and Head of the TGen Prostate Cancer Research Unit. "The discovery of mutations in this gene allows us the opportunity to explore a new path towards treating a significant number of men with advanced prostate cancer. As TGen's mission is to translate laboratory findings into the clinic, we hope to use this information to ultimately help provide prostate cancer patients more treatment options and a better quality of life."
The study was the result of an increasing trend in genome research: a massive international collaboration of scientists from several institutions. Large-scale collaborative studies like this are increasingly common in complex disorders that have a huge impact on public health, such as cancer, heart disease, diabetes, and mental disorders.
"This work reveals a new mechanism by which cancer cells can evade normal tissue architecture, which is a hallmark of tumor development," says noted Johns Hopkins University and Howard Hughes researcher Dr. Bert Vogelstein. "While further research is needed to reveal the full impact of EphB2 on prostate cancer, every step helps when fighting this disease."
According to Mousses, complex diseases such as prostate cancer involve more than one gene - often many - and a host of environmental factors, which makes them particularly hard to investigate.
In addition to researchers at TGen, the study involved researchers from the University of Turku in Finland, the National Human Genome Research Institute in Bethesda, MD, Tampere University of Technology in Finland, the Jewish General Hospital in Montreal, Quebec, Canada, Johns Hopkins University School of Medicine in Baltimore, MD, the University of Basel in Switzerland, Tampere University Hospital in Finland, and Mount Sinai Hospital in Toronto, Ontario, Canada.
Prostate cancer is cancer of the gland that makes part of a man's seminal fluid. The prostate is located in front of the rectum and under the bladder. The disease usually progresses slowly and may not require treatment for many years, but prostate cancer was responsible for the deaths of almost 31,000 US men in 2001. It is the second-leading cause of cancer death in US men (after lung cancer.) The American Cancer Society estimates that more than 230,000 cases of prostate cancer will be diagnosed in US men in 2004; 98 percent of these men will live for at least five more years.
About TGen
Established in 2002, TGen is a not-for-profit research institute whose primary mission is to make and translate genomic discoveries into advances in human health. Translational genomics research is a relatively new field employing innovative advances arising from the Human Genome Project to apply to the development of diagnostics, prognostics and therapies for cancer, neurological disorders, diabetes and other complex diseases. For additional information, please visit the TGen web site at www.tgen.org.
Journal
Nature Genetics