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Cancer sequencing project identifies potential approaches to combat aggressive leukemia
Date:1/11/2012

ents. Now we are working toward similar progress against this rare form of the disease," he said.

The human genome is the complete set of instructions needed to assemble and sustain human life. Leukemia and other cancers develop when normal cells accumulate mutations in the genome that cause the unchecked cell growth that is a hallmark of cancer. The three-year Pediatric Cancer Genome Project is sequencing the genomes of tumor cells and matched normal DNA samples of 600 children with some of the most poorly understood and aggressive cancers. Investigators believe the findings will be the foundation for the next generation of clinical tools.

For this study, researchers sequenced and analyzed the normal and cancer genomes of 12 St. Jude patients with ETP-ALL. Investigators then checked for some of the same mutations in an additional 94 young leukemia patients with either ETP-ALL or other types of T-cell ALL.

"We found mutations unique to ETP-ALL that are not seen in other forms of ALL," said co-author Richard Wilson, Ph.D., director of The Genome Institute at Washington University. "The results provide new targets for therapy and a way to use genetic tests to identify ETP-ALL patients early and earmark them for more aggressive therapy."

The pattern of mutations identified in ETP-ALL was reminiscent of changes associated with AML, Mullighan said. The alterations were concentrated in genes in the cytokine receptor and RAS signaling pathways that are involved in the type of cell regulation disrupted in cancer. The mutations, which included NRAS, FLT3, JAK3, IL7R and other genes, were found in about 67 percent of patients with ETP-ALL, but in only 19 percent of other T-ALL patients.

In addition, mutations in genes known or predicted to disrupt normal development of blood stem cells or lymphocytes were identified in 58 percent of ETP-ALL patients, but in just 17 percent of other T-ALL patients. The affected genes included ETV6, R
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Contact: Carrie Strehlau
media@stjude.org
901-595-2295
St. Jude Children's Research Hospital
Source:Eurekalert

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