Researchers at Upstate Medical University and Harvard University have linked the loss of key gene, WAVE1, to a lethal form of prostate cancer, according to a study published in the journal Oncotarget.
Prostate cancer is the most common form of cancer in men and is responsible for 27,000 deaths annually. About 220,000 new cases of prostate cancer are diagnosed each year.
Using bioinformatic meta-analysis to compare several publicly available databases, researchers found that alterations in the WAVE1 gene were associated with a shorter period of remission in patients who were treated for prostate cancer. Strikingly, the study also showed that 22.9 percent of the prostate cancers reviewed in the database harbored the WAVE1 gene deletion.
"We observed that prostate cancer tumors contain a frequent deletion of the WAVE 1 gene. What's important, though, is that this WAVE1 gene deletion occurs in metastatic and lethal cancer, thus suggesting that, the WAVE1 gene loss may represent an aggressive subtype of prostate cancer which is more challenging to treat and more likely to progress," said study coauthor Leszek Kotula, MD, Ph.D., associate professor of urology and biochemistry and molecular biology at Upstate Medical University in Syracuse, N.Y. "It is possible that patients who have tumors characterized by the deletion of the WAVE1 gene may benefit from earlier intervention, such as surgery or radiation therapy."
WAVE gene complexes are involved in cell motility and migration, cellular adhesion and cell-to-cell communication, numerous processes that can play a role in tumor progression and metastasis. "It is clear that disruption of the WAVE complex is associated with human cancers, including prostate cancer. However, what we have determined is that because lethal prostate cancers show this disruption, we may be able to identify mechanisms that lead to the tumor cell acquiring resistance to advanced therapies. Nonetheless, understanding the biological consequences of this deletion will require further investigation," said study coauthor Adam G. Sowalsky, Ph.D., instructor in medicine at Harvard Medical School.
The study, published in Oncotarget March 31, was funded by the National Institutes of Health and Department of Defense. Primary authors are Leszek Kotula, M.D., Ph.D., associate professor of urology and biochemistry and molecular biology; and Adam G. Sowalsky, Ph.D., instructor in medicine at Harvard Medical School. Other authors of the study include Dr. Pier Paolo Pandolfi, Dr. Steven Balk, Rachel Schaefer (Harvard Medical School, Boston, MA), and Dr. Gennady Bratslavsky and Rebecca Sager (Upstate Medical University, Syracuse, NY).
The study builds on earlier research (funded by the Department of Defense and the Kirby Foundation, Morristown, N.J.) by Kotula that implicated another gene, ABI1, as a tumor suppressor in prostate cancer. For the Oncotarget study researchers sought to find other genes that cooperate with ABI1 in the progression of prostate cancer, thus finding the WAVE1 gene as a culprit.
Kotula said his lab is now replicating the gene deletion in mice. Such work can aid in the development of drugs or new treatments to suppress tumors or provide more precision in the treatment of these aggressive cancers.
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