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Gene That Causes Childhood Cancer Neuroblastoma Is Found
Date:8/25/2008

rstand the genetic roots of this terrible disease, but also has led to dramatically new ideas for curative therapy."

The study team used high-speed, automated analytic equipment at the Center for Applied Genomics at Children's Hospital. By employing genome-wide scans to analyze DNA from the 10 most informative families with a history of neuroblastoma, Mosse and her colleagues first discovered that a region of chromosome 2 was associated with the disease. Further sequencing of that region identified mutations in the anaplastic lymphoma kinase (ALK) gene in eight families with familial neuroblastoma.

"This finding means that it is possible to offer simple, non-invasive screening for patients with a family history of neuroblastoma," said Mosse. She explained that ultrasound or a urine test could assist surveillance of children with an ALK mutation, so that if neuroblastoma appears, it can be detected at an early stage. "As we increase our knowledge of ALK mutations, we will also offer specialized diagnostic testing for all newly diagnosed patients with neuroblastoma, to eventually allow oncologists to better customize treatment to a child's genetic profile."

After detecting ALK mutations in familial neuroblastoma, the researchers then focused on the more common sporadic (non-familial) cases of neuroblastoma, and found that ALK mutations occurred in 12 percent of 194 tumor samples from the aggressive, high-risk form of the disease.

Although the normal role of the ALK gene is not well understood, other researchers had previously found that abnormalities in ALK raise a patient's risk for lymphoma and lung cancer. "We were the first to identify mutations in ALK," said Mosse, adding that in lymphoma and lung cancer, ALK acts through translocation, a different mechanism that involves an exchange of DNA between chromosomes to produce a new cancer-causing fusion gene.

In all three cancers, ALK acts as an oncogene, or cancer-causing gene; in f
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SOURCE The Children's Hospital of Philadelphia
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