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Mouse model improves understanding of clear cell sarcoma
Date:2/11/2013

(SALT LAKE CITY)Geneticists led by University of Utah Nobel Prize Laureate Mario R. Capecchi, Ph.D., have engineered mice that develop clear cell sarcoma (CCS), a significant step in better understanding how this rare and deadly soft tissue cancer arises. The mouse model also can potentially speed the development of drugs to target genes that must be activated for the cancer to form.

CCS arises in connective soft tissues, such as tendons, fat, blood vessels, and muscle. Researchers have known that the first step in the process that leads to CCS occurs when two human chromosomes, 12 and 22, randomly break after DNA gets damaged from the effects of sunlight or other causes. Each chromosome usually harmlessly rejoins after breaking. But occasionally part of one chromosome will join with part of the other to create a new gene called a fusion gene. When this gene, ews-atf1 is generated, it initiates the process that causes CCS.

The rare and aggressive nature of sarcomas, and their occurrence in children and young adults, long has interested Capecchi. In a study in the Feb. 11, 2013, online edition of Cancer Cell, he and colleagues from the University of Utah, the University of Texas M.D. Anderson Cancer Center in Houston, and Stanford University, describe how they developed the first mouse model of CCS by essentially recreating the human ews-atf1 gene in mice.

Capecchi, distinguished professor of human genetics and a Howard Hughes Medical Institute Investigator, says having a mouse model will teach researchers not only about CCS but also might provide an avenue for developing a drug that is more successful than current therapies. "Now that we have a mouse model for CCS, we can investigate what other events or gene mutations are required to form tumors," he says. "It also gives us the opportunity to investigate whether the CCS fusion gene might be a specific target for drugs."

Sarcomas often are removed by surgery, which
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Contact: Phil Sahm
phil.sahm@hsc.utah.edu
801-581-2517
University of Utah Health Sciences
Source:Eurekalert

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