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Gene That Causes Childhood Nerve Cancer Identified

by VR Sreeraman on August 25, 2008 at 4:02 PM
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 Gene That Causes Childhood Nerve Cancer Identified

Researchers have identified the hereditary gene mutations behind a deadly form of childhood cancer, opening the way to genetic tests in high-risk families, according to study released Sunday.

The same wayward gene has been previously linked to lymphoma and lung cancer in adults, so afflicted children could benefit from experimental drugs designed to suppress its activity, the study says.

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"This very important discovery not only helps us understand the genetic roots of this terrible disease, but also has led to dramatically new ideas for curative therapy," said lead researcher John Maris, head of the Center for Childhood Cancer Research at The Children's Hospital of Philadelphia.

Neuroblastoma attacks the nervous system. While fairly rare, it accounts for seven percent of all childhood cancers, and 15 percent of non-adult cancer deaths.
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The disease has long puzzled scientists because of its highly variable outcomes: some forms strike infants but then recede without treatment, while other variants, especially in older children, can be relentlessly aggressive.

"This discovery enables us to offer the first genetic tests to families affected by the inherited form of this disease," said Yael Mosse, lead author and a pediatric oncologist at Children's Hospital.

"Because there are already drugs in development that target the same gene in adult cancers, we can soon begin testing those drugs in children with neuroblastoma," she said.

An international team led by Maris scanned genomes -- the DNA library unique to every individual -- within 10 families beset by the disease.

The first broad scan narrowed the hunt to one particular chromosome, number 2. Another round of sequencing revealed that eight of the ten families had the same telltale variant in one spot, the anaplastic lymphoma kinase (ALK) gene.

The findings, published in the British journal Nature, will make it possible to use simple ultrasound or urine tests to monitor children with this mutation so that any signs of the cancer can be tackled at an early stage.

After pinpointing the source of familial neuroblastoma, the researchers asked whether the ALK mutations played a role in the so-called sporadic, or non-inherited, forms of the disease.

They found that it occurred in 12 percent of 194 tumor samples taken from a a particularly aggressive, high-risk variant.

Earlier research on lymphoma and lung cancer in adults had shown that ALK acts through a process called translocation in which DNA is exchanged across chromosomes to produce a fusion gene.

The Nature study is the first to identify a childhood cancer caused by mutations in a cancer-causing gene, according to the study.

Since the mutations discovered trigger an "on" signal for neuroblastoma cells, the abnormality is a prime target for therapies that block the ALK protein.

Several pharmaceutical companies are developing ALK inhibitors, and one is already in early-phase adult clinical trials against lung cancer and lymphoma.

"It's an advantage to be able to start with agents that have already been shown to be safe in adults," said Mosse.

Source: AFP
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