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Scripps Translational Science Institute Contributes to Discovery of Predisposition Gene for Childhood Cancer
Date:8/25/2008

SAN DIEGO, Aug. 25 /PRNewswire/ -- Researchers at Scripps Translational Science Institute (STSI) have contributed to a major genetic breakthrough -- the discovery of a gene responsible for the majority of inherited cases of a common childhood cancer. The finding was reported online Aug. 24 in Nature.

Neuroblastoma -- a cancer of the nervous system -- accounts for 15 percent of childhood cancer deaths and has bleak survival probabilities of less than 40 percent. There is a strong familial association and it was predicted more than 30 years ago that there is a genetic element to the disease.

The genetic discovery stems from a global research collaboration headed by Children's Hospital of Philadelphia. The study involved screening the genomes of 20 affected families (a total of 176 people), looking for single letter changes in the DNA code, which are mutations known as single nucleotide polymorphisms, or SNPs.

STSI was sought to participate in the study based on its expertise in conducting structural studies of SNPs identified in genes and proteins. Researchers at STSI looked at the mutations identified through the genetic screening and determined precisely where on the protein structure those mutations resided, enabling them to predict whether the mutations are likely to have meaningful biological effects.

Researchers identified inherited mutations in the gene encoding ALK, a tyrosine kinase receptor, as being responsible for causing the disease known as neuroblastoma in the majority of families. SNP mutations in this gene were also found in sporadic cases of neuroblastoma. The mutations mapped to a part of the ALK gene that cause it to be constantly active in promoting cell proliferation, explaining its ability to contribute to the cancer.

"This is a significant finding because it means we can screen for people who carry mutations to see if they are at risk for neuroblastoma," said Nicholas Schork, Ph.D., director of biostati
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SOURCE Scripps Translational Science Institute
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