FIGURE 4 from Temporary Knockdown of p53 During Focal Limb Irradiation Increases the Development of Sarcomas

Radiation-induced sarcomas exhibit an increase in proliferative gene programs and a decrease in myogenic differentiation programs. A, Heat map of the top 75 differentially expressed genes in radiation-induced sarcomas (n = 16) versus normal muscle (n = 7). Genes (rows) are colored by scaled, normalized expression values. Both rows and columns are clustered. B, Volcano plot of log₂ fold change for all genes with base mean greater than 50 in tumor (n = 16) versus normal (n = 7). Labeled genes have a nominal −log₁₀P value greater than or equal to 30. C, Normalized enrichment scores for all FDR significant pathways for GSEA of Hallmark pathways. Points are colored by −log₁₀ (nominal P value). D, Scatter plot comparing the differentially expressed pathways between tumors that arose in irradiated tissues (Rad) versus sporadic (Spor) tumors in mouse (y-axis) and human (x-axis) datasets. The EMT pathway is highlighted with a green dot. E, Boxplot showing gene expression of EMT pathway targets in mouse radiation-induced UPS compared with p53/RB tumors (top) and in human radiation-associated undifferentiated sarcomas compared with sporadic undifferentiated sarcomas.