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Comprehensive look at rare leukemia finds relatively few genetic changes launch disease
Date:7/27/2009

g's laboratory.

For this study, researchers analyzed leukemia cells from 111 St. Jude AML patients representing the seven most common subtypes of the disease. The scientists used several techniques to catalog the changes, including single-nucleotide-polymorphism (SNPs) microarrays to chart genome-wide regions of DNA gain or loss, which are known as copy number alterations (CNAs). To identify point mutations, the researchers also performed DNA re-sequencing of 25 genes that are commonly mutated in adult AML. Point mutations involve a single chemical change in the molecular building blocks of DNA.

The data demonstrated that, in contrast to pediatric acute lymphoblastic leukemia (ALL), AML is characterized by a very low burden of mutations. The researchers found slightly more than two CNAs per AML patient, and less than one point mutation per patient in the genes sequenced. The scientists also reported just 21 percent of AML patients had six or more lesions. By comparison, an earlier St. Jude study reported 77 percent of young ALL patients, a more common cancer, had that much DNA damage. Even more surprising, 34 percent of patients in this study lacked any apparent CNA, and 28 percent of those with a translocation lacked additional DNA abnormalities. Certain chromosomal re-arrangements are known as translocations.

The investigators also found no association between CNAs and patient outcome. Despite the low overall number of lesions in the patients studied, novel recurring regions of genetic alteration were identified that harbor known and potential new cancer genes.

The study also reports cryptic chromosomal translocations in 14 percent of patients in this study who, based on standard testing, appeared to lack such re-arrangements. Cryptic translocations are too small to be detected by conventional testing. Downing said the analysis identified focal CNAs adjacent to genes previously linked to chromosomal translocations. Those genes
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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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