Tanja[a]
Journal of the National Cancer Institute 2002;240-241,267-273.
Common Virus Linked to Childhood Brain Tumor
Tue Feb 19, 2002
By Faith Reidenbach
NEW YORK (Reuters Health) - A virus that commonly lies dormant in children may play a role in the formation of medulloblastomas, a type of childhood brain tumor, study findings show.
Some medulloblastomas contain one or two proteins from a little-known virus called the JC virus, scientists in Philadelphia have discovered. About 65% of children are infected with this virus by age 14, but in most cases the infection goes unnoticed because it doesn´t cause illness.
"Most people infected with JC virus are relatively healthy and are able to fight the virus," senior researcher Dr. Kamel Khalili of Temple University told Reuters Health. "However, for reasons we don´t fully understand, in some cases, the virus may be able to infect the cells in the brain which can turn into a medulloblastoma."
Khalili and colleagues have been studying the JC virus for almost 20 years, because in people with weak immune systems--such as those with AIDS--it is known to lead to a fatal nervous system disease. One thing they and other research groups have noticed is that when the virus is directly introduced into the brains of lab animals, several different types of brain tumors may develop.
Medulloblastomas are the second most common type of brain tumor in children, making up about 20% of cases. They grow fast and can spread widely throughout the body, and nearly half of all children affected with them die. Radiation exposure and certain genetic diseases are known to put children at risk, but in most cases the cause of medulloblastomas is a mystery.
When Khalili and his associates began studying these tumors, they found that a protein produced by the JC virus when it infects a cell was present in some medulloblastomas. Called T antigen, this protein is "a well-studied cancer-causing agent which also promotes virus replication," Khalili explained.
In the new study, the research team detected a second protein from the virus, called agnoprotein, in some medulloblastomas. The function of agnoprotein is unknown. Specifically, the researchers examined tumor samples from patients between the ages of 3 and 18. In 11 of 16 samples (69%), they found the gene that produces agnoprotein, and in seven of those samples (44%), the gene that produces T antigen was also present.The findings are published in the February 20 issue of the Journal of the National Cancer Institute.
The fact that agnoprotein occurs in some medulloblastomas without T antigen suggests that it has a role in the development of the tumors, the research group suggests. Also, it is known that "the agnoprotein has the capacity to associate with the T antigen," Khalili said in a university press release. "So it seems that the communication between these two viral proteins may impact the ability of the virus to induce brain tumors." Further study is needed to see if that´s true, he said. The presence of the JC virus in the tumors might just be a coincidence.
Still, Khalili added in the interview with Reuters Health, "if we are able to prove that the virus plays a significant role, then we can develop therapeutic vaccines against T-antigen and agnoprotein." Such vaccines could conceivably prevent the JC virus from inducing the formation of medulloblastomas.
In a commentary, Dr. Howard Fine of the National Cancer Institute expressed doubt about the importance of agnoprotein in the development of medulloblastomas. T antigen "still remains the most likely culprit," he says, because of its known role in suppressing certain cancer-related proteins.
And even T antigen may not have a role in medulloblastoma development, according to Fine. He explains that the cancer-related proteins it suppresses "are rarely, if ever," found in human medulloblastomas except when there is a known cause such as radiation exposure. Also, studies show that monkeys and other primates do not develop medulloblastomas when they are infected with JC virus.
More study is needed to look for the presence of JC virus in normal brain tissue as well as in other types of brain tumors, Fine concludes.