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Tumors evolve rapidly in a childhood cancer, leaving fewer obvious tumor targets
Date:1/20/2013

An extensive genomic study of the childhood cancer neuroblastoma reinforces the challenges in treating the most aggressive forms of this disease. Contrary to expectations, the scientists found relatively few recurrent gene mutationsmutations that would suggest new targets for neuroblastoma treatment. Instead, say the researchers, they have now refocused on how neuroblastoma tumors evolve in response to medicine and other factors.

"This research underscores the fact that tumor cells often change rapidly over time, so more effective treatments for this aggressive cancer will need to account for the dynamic nature of neuroblastoma," said study leader John M. Maris, M.D., director of the Center for Childhood Cancer Research at The Children's Hospital of Philadelphia (CHOP).

Striking the peripheral nervous system, neuroblastoma usually appears as a solid tumor in a young child's chest or abdomen. It comprises 7 percent of all childhood cancers, but causes 10 to 15 percent of all childhood cancer-related deaths. Neuroblastoma is notoriously complex, with a broad number of gene changes that can give rise to the disease.

Maris headed the multicenter research collaborative, the TARGET (Therapeutically Applicable Research to Generate Effective Treatments) initiative, which released its findings today in Nature Genetics. This largest-ever study genomic study of a childhood cancer analyzed DNA from 240 children with high-risk neuroblastomas. Using a combination of whole-exome, whole-genome and transcriptome sequencing, the study compared DNA from tumors with DNA in normal cells from the same patients.

Researchers at CHOP and other centers previously discovered neuroblastoma-causing mutations, such as those in the ALK gene. In the subset of patients carrying this mutation, oncologists can provide effective treatments tailored to their genetic profile.

"A few years ago, we thought we would be able to sequence the genome
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Contact: Rachel Salis-Silverman
salis@email.chop.edu
267-426-6063
Children's Hospital of Philadelphia
Source:Eurekalert

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