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Virus Might Be Linked to Childhood Brain Cancer

Common bug may spur malignant medulloblastomas

FRIDAY, Feb. 22, 2002 (HealthDayNews) -- Researchers have detected a protein produced by a common virus in human brain tumors, raising the possibility that the virus plays a role in the development of the most common malignant brain cancer in children.

Though the virus protein has been shown to cause tumors in animal models, this is the first time it has been seen in human tumors, which in this case are deadly medulloblastomas.

The researchers' findings appear in the latest issue of the Journal of the National Cancer Institute.

The virus in question is a human neurotropic polyomavirus called JCV, which is present in at least 65 percent of humans worldwide by the time they reach the age of 14.

Usually, the virus remains dormant. In certain cases, though -- most notably when there is immune suppression of some sort -- it can cause progressive multifocal leukoencephalopathy (PML), a fatal neurological disease similar to multiple sclerosis and often seen in AIDS patients. The current research suggests JCV may also stimulate the growth of cancerous tumors.

Scientists aren't sure how JCV is transmitted, but believe parents may pass it to children via the upper respiratory tract.

There is a further mystery surrounding how the viral protein, lodged in a child, is triggered.

"I think some transient immune suppressive condition might activate the viral genome," says Kamel Khalili, lead author of the paper and director of the Center for Neurovirology and Cancer Biology at Temple University College of Science and Technology in Philadelphia. "There also may be some genetic component that makes them susceptible, and maybe a combination of genetic and environmental factors can induce the tumor in these patients."

Medulloblastomas are the second most common brain tumors in children -- and the most common malignant tumors -- and they are difficult to treat. Typically, surgery and chemotherapy are used and, depending on the age of the child, radiation treatments are sometimes given. Currently, about half of the children who develop this malignant tumor will die from it. Although some subsets of the tumor are easier to treat than others, even curable tumors carry a risk of serious long-term side effects, says Dr. Ira Dunkel, assistant attending pediatrician at Memorial Sloan-Kettering Cancer Center in New York City.

"Our understanding of the mechanisms of the tumor is still pretty primitive, and studies like this -- that give clues about how medulloblastomas are developing or progressing -- will hopefully lead us towards better and less toxic therapies," Dunkel says.

Previous experiments had shown that genes expressed from viral proteins cause cancer in a broad range of laboratory animals.

"When you find that the JCV genome is present in human cancer and that those proteins that have induced disease in animals also exist in human brain tumors, you are led to believe that the virus might cause tumors in pediatric patients," says Khalili. "It is alarming because we know that 75-plus percent of the human population is infected with the virus."

"Unfortunately, we don't know whether these are occasional findings because this virus can be present in the whole population and may have nothing to do with the tumor, or whether this virus is actually the cause," says Dr. Antonio Iavarone, an associate professor of neurology at the Albert Einstein College of Medicine. "The only way to know that would be a large epidemiologic study, and until that is done it's very difficult to know if the virus has something to do with the tumors."

If, in fact, it does turn out that the virus is responsible for the tumor, the next step would be to find out how the virus enters the tumor pathway -- and then look for ways to stop it.

Khalili envisions a therapeutic vaccine to help combat medulloblastomas in children; his laboratory is already in the process of developing an experimental vaccine.

However, that's far down the line.

"The study is very provocative and certainly deserves attention, but unfortunately it doesn't solve any big issues so far," Iavarone says. "We clearly need more data to understand the role of the virus."

What To Do: For more information on pediatric cancer, visit the Pediatric Oncology Resource Center or Memorial Sloan-Kettering's Pediatric Cancer Care site.

SOURCES: Interviews with Kamel Khalili, Ph.D., director and professor, Center for Neurovirology and Cancer Biology, Temple University College of Science and Technology, Philadelphia; Ira Dunkel, M.D., assistant attending pediatrician, Memorial Sloan-Kettering Cancer Center, New York City; Antonio Iavarone, M.D., associate professor, department of neurology, Albert Einstein College of Medicine, Bronx, N.Y.; Feb. 20, 2002, Journal of the National Cancer Institute
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