Key result
In a TP53-deficient rat model, angiosarcomas showed upregulation of cell cycle and DNA replication pathways and downregulation of metabolic pathways compared to other tissues.
Why the study?
Sarcomas have poor prognosis and treatment outcomes have not significantly improved, prompting the characterization of specific gene expression patterns of angiosarcomas with loss of TP53 function in a rat model.
This preclinical study characterizes the gene expression profile of TP53-deficient angiosarcomas in a rat model, highlighting significant alterations in cell cycle and metabolic pathways.
Remains hypothesis-generating in a rat model; leaves open translation to human angiosarcoma therapy.
Sarcomas are a heterogeneous group of malignant tumors, that develop from mesenchymal cells. Sarcomas are tumors associated with poor prognosis and expected short overall survival. Efforts to improve treatment efficacy and treatment outcomes of advanced and metastatic sarcoma patients have not led to significant improvements in the last decades. In the Tp53C273X/C273X rat model we therefore aimed to characterize specific gene expression pattern of angiosarcomas with a loss of TP53 function. The presence of metabolically active tumors in several locations including the brain, head and neck, extremities and abdomen was confirmed by magnetic resonance imaging (MRI) and positron emission tomography (PET) examinations. Limb angiosarcoma tumors were selected for microarray expression analysis. The most upregulated pathways in angiosarcoma vs all other tissues were related to cell cycle with mitosis and meiosis, chromosome, nucleosome and telomere maintenance as well as DNA replication and recombination. The downregulated genes were responsible for metabolism, including respiratory chain electron transport, tricarboxylic acid (TCA) cycle, fatty acid metabolism and amino-acid catabolism. Our findings demonstrated that the type of developing sarcoma depends on genetic background, underscoring the importance of developing more malignancy susceptibility models in various strains and species to simulate the study of the diverse genetics of human sarcomas.
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Smyczyńska et al. (2020) studied Angiosarcoma with loss of TP53 function. TP53-deficient angiosarcoma vs. All other tissues was evaluated on Gene expression pattern (upregulated and downregulated pathways). In a TP53-deficient rat model, angiosarcomas showed upregulation of cell cycle and DNA replication pathways and downregulation of metabolic pathways compared to other tissues.
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