Navigate Up

UPMC/University of Pittsburgh Schools of the Health Sciences
Senior Manager
Telephone: 412-578-9193 or 412-624-3212
Patients and medical professionals may call 1-800-533-UPMC (8762) for more information.

University of Pittsburgh Schools of the Health Sciences

‚ÄčUniversity of Pittsburgh Study Reports First-Ever Discovery of Genetic Shut Down Trigger in Healthy Immune Cells

PITTSBURGH, May 9, 2007 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.

The study was funded by the National Cancer Institute.

For copies of the paper, visit http://www.plosone.org/home.action.

 

©  UPMC | Affiliated with the University of Pittsburgh Schools of the Health Sciences
Supplemental content provided by A.D.A.M. Health Solutions. All rights reserved.

For help in finding a doctor or health service that suits your needs, call the UPMC Referral Service at 412-647-UPMC (8762) or 1-800-533-UPMC (8762). Select option 1.

UPMC is an equal opportunity employer. UPMC policy prohibits discrimination or harassment on the basis of race, color, religion, ancestry, national origin, age, sex, genetics, sexual orientation, marital status, familial status, disability, veteran status, or any other legally protected group status. Further, UPMC will continue to support and promote equal employment opportunity, human dignity, and racial, ethnic, and cultural diversity. This policy applies to admissions, employment, and access to and treatment in UPMC programs and activities. This commitment is made by UPMC in accordance with federal, state, and/or local laws and regulations.

Medical information made available on UPMC.com is not intended to be used as a substitute for professional medical advice, diagnosis, or treatment. You should not rely entirely on this information for your health care needs. Ask your own doctor or health care provider any specific medical questions that you have. Further, UPMC.com is not a tool to be used in the case of an emergency. If an emergency arises, you should seek appropriate emergency medical services.

For UPMC Mercy Patients: As a Catholic hospital, UPMC Mercy abides by the Ethical and Religious Directives for Catholic Health Care Services, as determined by the United States Conference of Catholic Bishops. As such, UPMC Mercy neither endorses nor provides medical practices and/or procedures that contradict the moral teachings of the Roman Catholic Church.

© UPMC
Pittsburgh, PA, USA UPMC.com