Candidate sarcoma targets.

141 sarcoma-relevant genes were identified by transcriptional profiling of genetically engineered Kras-driven mouse sarcomas [6]. Their contributions to sarcoma growth were probed by customized shRNA screening using 5 shRNAs per candidate gene. Control shRNAs were directed against LUC, RFP and LACZ; shKras served as a positive control [5]. (A) Five candidate genes whose targeting by shRNAs in this screen resulted in reduced sarcoma cell proliferation represent potentially druggable genes/ cellular processes: Asns, Ube2c, Cenpe, Has2, Creb3l2. The anti-proliferative effects of the shRNAs directed against these candidate genes in a Kras;CDKN2A^null mouse RMS cell line are shown. (B) Effective knockdown by the target-specific shRNAs in Kras;CDKN2A^null mouse RMS cells was confirmed by qRT-PCR. Target gene expression was determined by gene-specific qRT-PCR (mean +/- SD of 3 technical replicates presented; ns p≥0.05, * p<0.05, ** p<0.01, *** p <0.001, as determined by T-tests compared to cntrl-shRNA infected cells).