Skip to: site menu | section menu | main content
University of Pittsburgh discovers genetic 'shut down' trigger ...
A fundamental genetic mechanism that shuts down an important gene in healthy immune system cells has been discovered that could one day lead to new therapies against infections, leukemia and other cancers.
Results of a University of Pittsburgh School of Medicine study on the mechanism,
called a somatic stop-codon mutation, are being reported today in the online
journal PLoS ONE, published by the Public Library of Science.
"This kind of loss-of-function mutation can be very dangerous, and it is
the first such mutation that has been identified in normal immune cells in blood," said
Bora E. Baysal, M.D., Ph.D., assistant professor of obstetrics, gynecology and
reproductive sciences at the University of Pittsburgh School of Medicine. "We
did control experiments for two years to make sure it was real and not a technical
error."
Dr. Baysal and his colleagues tested 180 samples, including blood from healthy
individuals and other material from those with childhood leukemia, looking at
specific portions of DNA in immune cells known as monocytes, natural killer cells
and lymphocytes. These cells are key to the body’s immune response against
infection and disease. The investigators found somatic stop-codon mutations in
an average of 5.8 percent of crucial portions of genetic material that deliver
instructions from DNA, called messenger RNA, in normal blood samples and in a
quarter of leukemia samples.
"DNA is the blueprint for all living cells. It carries the genetic code
for most biological functions and is passed virtually unchanged from generation
to generation," said Dr. Baysal, who also is an associate investigator at
the university-affiliated Magee-Womens Research Institute. "Harmful alterations
in the code ‘ mutations’can produce genetic disorders and play an
important role in the development of cancer. Normal cells such as monocytes,
lymphocytes and natural killer cells have many mechanisms to recognize and repair
mutations, but a stop-codon mutation is a kind of permanent "off" switch
that has escaped DNA repair," he added.
"We believe there is a good biological reason for this. It may allow the
cells to survive in a low-oxygen environment, such as where there is cancer or
infection," said Dr. Baysal. "It is part of the process for immune
cells to ‘armor up’ for battle against cancer cells and other diseases."
Earlier research on the mutated gene suggests the stop-codon mutation might be
part of the programmed adaptive response to oxygen deprivation. This mutation
and its location is "unusual because it predicts loss-of-function, it targets
a classical tumor-suppressor gene, and it occurs in (peripheral blood mononuclear
cells)," Dr. Baysal wrote, adding that the mutation is present at much higher
levels in messenger RNA compared to DNA.
"This may give us a tool to modify the immune cells’ survival in a
low oxygen environment, which could help the cells to survive and fight infections
and tumors," said Dr. Baysal, calling the mutated gene a potential "therapeutic
target."
University of Pittsburgh Schools of the Health Sciences
NOTE: This web site is designed for educational purposes only and is not engaged in rendering medical advice. The information provided through this site should not be used for diagnosing or treating a health problem or a disease. If you have or suspect you may have a health problem, you should consult your health care provider