A dramatically better computer tool for finding the genetic missteps that fuel cancer has been developed by St. Jude Children's Research Hospital Washington University Pediatric Cancer Genome Project investigators. Researchers are using the new algorithm to help identify the chromosomal rearrangements and DNA insertions or deletions unique to cancer.
The new computational method is known as CREST, short for Clipping Reveals Structure. Using CREST, researchers identified 89 new structural differences in the cancer genomes of five St. Jude patients with a subtype of acute lymphoblastic leukemia (ALL) known as T-lineage ALL. CREST revealed complex chromosomal rearrangements, including one that involved four chromosomes. Investigators also used the tool to find 50 new variations in melanoma cells. Melanoma is the most serious form of skin cancer. The study appears in the June 12 advance online edition of the scientific journal Nature Methods.
"CREST is significantly more accurate and sensitive than existing methods of finding structural variations in next-generation sequencing data. It finds differences between a patient's normal and cancer genomes other tools cannot find," said Jinghui Zhang, Ph.D., an associate member of the St. Jude Department of Computational Biology. She is the study's senior author. "Similar tools miss up to 60 to 70 percent of these structural rearrangements in tumors. CREST ensures that scientists will be able to find important structural variations that play critical roles in tumor formation."
Zhang said the need for new ways to identify the genomic variations that lead to cancer became clear shortly after the genome project began. The St. Jude Washington University collaboration was launched in 2010 to sequence and compare the complete normal and cancer genomes of 600 young patients battling some of the most challenging forms of the disease. Organizers expect the three-year effort to revolutionize understandin
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St. Jude Children's Research Hospital