|
Last Updated: Dec 27th, 2006 - 19:07:47 |
More than 50 percent of the prostate cancer cases result from two new fusion genes, TMPRSS2-ERG and TMPRSS2-ETV1 within a prostate cell, according to a study published in the Oct. 28, issue of Science. This is a finding that may lead to tools for diagnosis and treatment of prostate cancer and potentially other diseases.
The study, led by Arul Chinnaiyan, M.D. Ph.D. at the University of Michigan Medical School, found the non-random, recurrent rearrangements gene arrangement of separate genes in more than 50 percent of prostate cancer samples.
The researchers believe the fused genes overproduce proteins that stimulate growth of cancer cells.
"The data in our study provides tantalizing evidence that gene fusion is the causative agent - the initiating event - in prostate cancer," said Dr. Chinnaiyan. "It's what drives the aberrant over-expression of cancer-causing genes and is the first step in the progression of tissue changes leading to prostate cancer."
Prostate cancer is common among US men, second only to skin cancer. According to the American Cancer Society, about 232,090 new cases will be diagnosed in 2005, and approximately 30,350 men will die of prostate cancer.
To screen for prostate cancer, doctors perform a test for prostate-specific antigen (PSA), a protein in the blood. However, the PSA screening test is unreliable. Many other reasons may raise the PSA in cancer-free individuals, causing false positive results.
The current finding may offer an alternative. A diagnostic test of blood or urine based on the fused genes (or their protein products) would be far more specific for prostate cancer and accurate than the PSA test, according to Chinnaiyan.
Although the researchers do not know exactly what causes the gene fusion that is responsible for prostate cancer, they do know that one gene moving from one part of DNA to another (a phenomenon known as translocation) can affect over-expression of certain genes resulting in cancers.
It has been known that gene rearrangements are involved in leukemia, lymphoma and soft-tissue cancers. One example of translocation involves the fusion of the BCR gene and the ABL gene. The resulting BCR-ABL fusion gene causes the development of chronic myelogenous leukemia, according to the National Cancer Institute.
In the new study, researchers found two proteins were overproduced in 57 percent of 167 prostate cancer patients. These proteins, absent in the 57 prostate samples without cancer, were under the control of two genes known as ETV1 and ERG. The two genes were previously found to inflict a rare bone cancer called Ewing's sarcoma, in addition to other cancers after genetic rearrangement.
The abnormal gene fusion associated with prostate cancer occurs when one of two genes (ERG or ETV1) merges with a prostate-specific gene called TMPRSS2, forming fusion genes, TMPRSS2-ERG and TMPRSS2-ETV1, according to the study.
Previous studies at the University of Michigan, involving 22 prostate cancer samples, resulted in 20 samples (91 percent) showing over-expression of ERG or ETV1, and they also showed fusion with the TMPRSS2 gene. This indicates that fusion of ERG or ETV1 with TMPRSS2 gene causes the gene expression.
"This finding may have important implications for the understanding of the prostate cancer disease process and the development of potential therapies to arrest this process," said Dr. Chinnaiyan,
Although genetic rearrangements were known to occur in leukemia, lymphoma, and soft tissue sarcomas, the gene fusion involved in the prostate cancer is most common among human malignancies, according to the National Cancer Institute.
The researchers suggested that other unknown types of gene rearrangement involving TMPRSS2 may also play a role in the development of prostate cancer.
Scott Tomlins, a U-M graduate student in pathology and first author of the Science paper, said 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 said.
Discovery of TMPRSS2-ERG and TMPRSS2-ETV1 fused genes would offer a target for the development of new drugs. If scientists could find a drug to block the genes, it could be the basis for a new, effective treatment for prostate cancer.
This study is the first evidence that non-random, recurrent rearrangements of genes can occur in epithelial tumors, such as prostate cancer, according to the National Cancer Institute.
"Studying gene alterations in prostate cancer is difficult," said Jacob Kagan, Ph.D., program director for the study. "As a result there has never been a clear identification of recurrent, non-random genetic rearrangements. This finding is an important advance because it suggests that similar mechanisms may be involved in other epithelial cancers such as breast, lung, and colon."
© 2004-2005 by foodconsumer.org unless otherwise specified
Top of Page
|
