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Washington University scientists first to sequence genome of cancer patient
Date:11/5/2008

tients age. According to the American Cancer Society, the five-year survival rate for AML is 21 percent.

Despite advances in the genetic understanding of many cancers, scientists have learned very little about the genetic basis of AML. "After years of genetic studies of AML looking at genes of interest, we were getting no closer to uncovering the molecular underpinnings of the disease," Ley says. "We felt that with new genome sequencing technology, now was the time to take a whole-genome approach."

Based on genetic testing with traditional methods at the study's outset, the patient was known to have two mutations that are common among AML patients, an indicator she had a typical subtype of the disease, and one of the many reasons why her genome was selected for sequencing.

The researchers sequenced the patient's full genome, meaning DNA from both sets of chromosomes, using genetic material obtained from a skin sample. This gave the scientists a reference DNA sequence to which they could compare genetic alterations in the patient's tumor cells, taken from a bone marrow sample that was comprised only of tumor cells. Both samples were obtained before the patient received cancer treatment, which can further damage DNA.

The scientists then looked for genetic differences - points of single base changes in the DNA - in the patient's tumor genome compared with her normal genome. Of the nearly 2.7 million single nucleotide variants in the patient's tumor genome, almost 98 percent also were detected in DNA from the patient's skin sample, thus narrowing the number of variants that required further study to about 60,000.

Using sophisticated software and analytical tools, some of which the researchers developed specifically for this project, they identified the 10 mutations (including the two previously known genetic mutations that are common to her leukemia subtype but do not directly cause the disease) by looking for single base DNA
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Contact: Caroline Arbanas
arbanasc@wustl.edu
314-286-0109
Washington University School of Medicine
Source:Eurekalert  

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