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Ewing's sarcoma: general insights from a rare model
1Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Abstract:
Ewing's sarcoma is characterized by the presence of fusion oncoproteins involving EWSR1 and an ETS gene, most commonly FLI1. In this issue of Cancer Cell, Smith et al. have combined RNA interference with expression profiling to study the pattern of gene expression downstream of the most common of these fusions, EWS/FLI. Using this strategy, Smith et al. have identified a homeobox gene, NKX2.2, which is both highly expressed in Ewing's sarcoma and essential for the transforming activity of EWS/FLI.
Insights
Researchers identified NKX2.2 as a key gene in Ewing
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Ewing's sarcoma is a bone and soft tissue cancer.
- It is defined by EWSR1-ETS gene fusions, typically EWSR1-FLI1.
Purpose of the Study:
- To investigate gene expression patterns regulated by the EWS/FLI fusion.
- To identify genes critical for the oncogenic activity of EWS/FLI.
Main Methods:
- RNA interference was used to silence genes.
- Expression profiling was employed to analyze gene activity.
Main Results:
- The homeobox gene NKX2.2 was found to be highly expressed in Ewing's sarcoma.
- NKX2.2 is crucial for the transforming capabilities of the EWS/FLI oncoprotein.
Conclusions:
- NKX2.2 is a significant downstream target of EWS/FLI in Ewing's sarcoma.
- Targeting NKX2.2 may offer a therapeutic strategy for Ewing's sarcoma.

