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Genes May Raise Risk of Neuroblastoma in Kids
Date:6/17/2009

Finding sheds light on cause of lethal cancer, expert says,,,,

WEDNESDAY, June 17 (HealthDay News) -- Researchers have identified a genetic trait that appears to boost the risk that a child will develop an often-fatal cancer that targets the nervous system.

The findings don't point toward a treatment, but they do give scientists more insight into neuroblastoma, said study co-author Dr. John Maris.

"We've learned a lot more about the underlying cause and the biology of the disease," said Maris, director of the Center for Childhood Cancer Research at the University of Pennsylvania School of Medicine, in Philadelphia.

Although not well known, neuroblastoma is the second most common form of cancer in children after leukemia, Maris said. The American Cancer Society estimates that about 650 children develop it each year in the United States.

Neuroblastoma strikes young children and infants, and is fatal in about two-thirds of the cases, Maris said.

Tumors develop in the nervous system and can appear along the spine and in the neck, chest and abdomen, he said. Many tumors begin in the adrenal gland, which produces adrenaline in the body.

Most children have an aggressive form of the disease and must be treated with intensive therapy, involving strategies such as chemotherapy, radiation and stem-cell transplants, Maris said.

The disease appears to run in families, but only in about 1 percent of cases, he said. In those cases, a child survives the cancer and grows up to have a child with the disease.

In the new study, researchers looked at genetic samples from hundreds of white children with the disease and compared them with those of children who didn't have it.

They found that a specific "copy number variation" -- a kind of genetic trait -- doubles the chances that a child will develop the cancer. A report on the findings appears in the June 18 issue of Nature.

People inherit half their DNA from their mothers and half from fathers, but errors occur along the way. Human's genetic replication machinery functions, in a sense, like a malfunctioning copy machine that occasionally spits out too many -- or two few -- copies of a page while duplicating a stack of documents.

When DNA is copied incorrectly, the result is known as a copy number variation.

Maris acknowledged that the value of the research is limited. "We hope that some day it may give us information that will lead to new therapy," he said, but the findings won't lead to a genetic test for the illness.

After all, the cancer strikes just one in 7,000 new births, and a doubling of that risk isn't hugely significant, he said.

In the future, however, researchers might better understand how genetic variations work together to cause the cancer. "Once we have that," he said, "we'll have a more precise estimate of the likelihood of developing the disease."

Dr. John S. Yu, director of surgical neuro-oncology at Cedars-Sinai Medical Center in Los Angeles, agreed that the findings hold promise.

"This is a small step of many steps, and potentially a very important step, in determining the cause of a pretty lethal cancer," Yu said.

In another study in the same issue of Nature, researchers from the New York University School of Medicine reported they had discovered a protein receptor on the outer surface of cells that's involved in the spread of leukemia.

Specifically, they looked at T-cell acute lymphoblastic leukemia, which strikes mostly children. Though treatable, the relapse rate for this cancer is high and, once it recurs, it is seldom treatable, experts say, because it invades the brain and spinal cord.

In a study on mice, the researchers found that "if you knock out this receptor, these cells will not go to the brain under any circumstances," study senior author Ioannis Aifantis, co-director of the Cancer Stem Cell Program at the NYU Cancer Institute, said in a statement.

The finding could lead to the development of new drugs that would block the receptor and prevent relapse, the researchers added.

More information

The American Cancer Society has more on neuroblastoma.



SOURCES: John Maris, M.D., director, Center for Childhood Cancer Research, and chief, Division of Oncology, University of Pennsylvania School of Medicine and Children's Hospital of Philadelphia; John S. Yu, M.D., director, surgical neuro-oncology, Cedars-Sinai Medical Center, Los Angeles; June 18, 2009, Nature; June 17, 2009, news release, New York University Langone Medical Center


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