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NIH scientists map gene changes driving tumors in common pediatric soft-tissue cancer
Date:1/23/2014

ex molecular events that occur in tumor cells, compare normal DNA with tumor DNA, identify mutations in genes, and determine exactly which genes are turned on (activated) or turned off (deactivated), leading to progression of this cancer.

Through their studies, they identified two distinct genotypes of rhabdomyosarcoma tumors. The first genotype is characterized by either a PAX3 or PAX7 fusion gene; a fusion gene is a gene made by joining parts of two different genes. The second genotype lacks a PAX fusion gene but harbors mutations in key signaling pathways; a signaling pathway is a group of proteins that work together to regulate one or more cell functions, such as cell division or cell death.

The researchers also found that, as in other types of pediatric cancers, the overall number of alterations in tumor DNA that develop over the children's lifespan (known as somatic mutations) were relatively low compared to DNA alterations that children were born with. The somatic mutation rate was especially low in tumors with a PAX fusion gene. Nevertheless, they did find relatively frequent somatic mutations in several genes, including NRAS, KRAS, HRAS, FGFR4, PIK3CA, CTNNB, all of which had previously been found to be mutated in rhabdomyosarcoma, as well as the genes FBXW7 and BCOR, which had not been previously associated with this disease.

Moreover, they identified mutations in additional genes in the RAS/PIK3CA signaling pathway. Overall, alterations in this pathway were found in 93 percent of rhabdomyosarcoma tumors. Intriguingly, many of the genes mutated in the tumors that did not have a PAX fusion gene were found to be turned on or off by proteins produced by PAX fusion genes.

"Although more work is needed, our study may provide researchers with the rationale to develop genomics-guided therapeutic interventions with greater efficacy and fewer side effects than the treatments options currently available for pediatric patients wi
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Contact: NCI Press Officers
ncipressofficers@mail.nih.gov
301-496-6641
NIH/National Cancer Institute
Source:Eurekalert

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