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

is followed by radiation or chemotherapy. If the fusion gene turns out to be a viable drug target, Capecchi cautions, it could take a decade or longer before it's available to those with the disease.

Information from the National Cancer Institute estimated that 11,280 U.S. residents would be diagnosed with the disease in 2012, with approximately 3,900 people expected to die. Estimated mortality rates of CCS vary, but it is considered an aggressive cancer, with a five-year mortality rate of approximately 80 percent. In the United States, CCS accounts for around 7 percent of cancers among children, adolescents, and young adults under age 20, according to the National Cancer Institute.

To make the mouse model of CCS, Capecchi and his colleagues had to create the ews-atf1 fusion gene in mice. For this they employed the technique he developed and in 2007 was awarded the Nobel Prize in physiology or medicine for: gene targeting.

They manipulated the process by which a gene found in every mouse cell, rosa26, receives the instructions that determine its function. Called transcription, this process, is initiated by a region of DNA, known as a promoter, on the same chromosome as rosa26. Capecchi and his team used a molecular agent to interrupt the transcription process and induce the promoter to instead make the fusion gene on command of the enzyme that activates it. To turn on the fusion gene, this enzyme, Cre, also must be activated, and to do that the researchers used tamoxifenthe same molecule in cancer drugs. To introduce Cre into cells, Capecchi used a small sequence of HIV as a vehicle for the enzyme to enter mouse cells that contained the fusion gene.

Although different cell types could give rise to this cancer, Capecchi identified mesenchymal stem cells, which can create a large number of tissue types, including the soft tissue where sarcomas form, as being especially good for producing CCS tumors. To activate the fusion gene, Cr
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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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