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Researchers improve method for finding genetic mistakes that fuel cancer
Date:6/12/2011

g of childhood malignancies and lay the foundation for new treatments to cure or prevent cancer, which remains the leading cause of death by disease in American children and adolescents.

The human genome is the complete set of instructions for guiding an individual's development and continuing function. Those instructions are encoded in the approximately 3.1 billion bases of DNA, which are arranged into the genes and the chromosomes found in almost every cell. The genome project takes advantage of next-generation sequencing technology, which reduced the cost and time needed to determine the order of the four chemical bases that make each person's DNA unique. If that order is disrupted, cancer can result.

Next-generation sequencing technology breaks the long, double-stranded DNA molecule into millions of smaller fragments, which are each copied about 30 times. Using a reference human genome as a template, those segments are then reassembled according to rules that govern interaction of DNA's four chemical bases; adenine, thymine, cytosine and guanine. Those rules dictate adenine pairs only with thymine and cytosine only with guanine. For this project, investigators are interested in where a patient's normal and cancer genomes differ. Researchers believe those differences include cancer's origins.

Zhang and her colleagues began work on CREST when they manually detected a chromosomal rearrangement involving a known cancer gene that existing analytic tools failed to detect.

In developing CREST, researchers turned to pieces of DNA known as soft clips. These are the DNA segments produced during sequencing that fail to properly align to the reference human genome as the patient's genome is reassembled.

"Portions of the soft clip align nicely, but other portions just do not go together with the reference human genome," Zhang said, noting that although soft clips can be caused by chromosomal rearrangement, they have many causes a
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Contact: Summer Freeman
summer.freeman@stjude.org
901-595-3061
St. Jude Children's Research Hospital
Source:Eurekalert

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