These sarcomas identified a cluster of genes upregulated in mouse sarcomas and human RMS compared to normal skeletal muscle.
We identified a geneset in the mouse sarcomas that is highly enriched in human MFH.
However, our finding of a sarcoma geneset conserved between mouse sarcomas and human MFH suggests that this subtype of human sarcoma shares an underlying biology beyond a common histologic appearance.
Functional genomic screening of genetically engineered mouse sarcomas revealed that asparagine synthetase (ASNS) exerted the strongest observed effect on sarcoma cell proliferation within a small group of genes upregulated in both mouse and human sarcomas.
OF carried out pathology analysis for mouse sarcomas and aided in figure preparation.
For mouse sarcomas, 64 tumors annotated for metastatic outcome were utilized (met, N=25; non-met, N=39).
Instead, the screen was designed to evaluate the functional contributions of a particular group of sarcoma signature genes that were expressed at higher levels in both Ras-driven mouse sarcomas and human sarcomas.
We hypothesized that genes most differentially expressed between mouse sarcoma and normal muscle would provide a useful molecular signature to interrogate human sarcoma datasets (Fig. 1A).
The inhibition of extracts on the growth of transplanted mouse sarcoma S180 in mice is shown in Figure 2.
Finally, genetic silencing of ASNS in mouse sarcoma cells combined with depletion of plasma asparagine inhibited tumor growth in vivo.
