TP53-Deficient Angiosarcoma Expression Profiling in Rat Model

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 t...

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Bibliographic Details
Main Authors: Urszula Smyczyńska, Damian Strzemecki, Anna M. Czarnecka, Wojciech Fendler, Michał Fiedorowicz, Marlena Wełniak-Kamińska, Magdalena Guzowska, Kamil Synoradzki, Łukasz Cheda, Zbigniew Rogulski, Paweł Grieb
Format: Article
Language:English
Published: MDPI AG 2020-06-01
Series:Cancers
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Online Access:https://www.mdpi.com/2072-6694/12/6/1525
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Summary: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 <i>Tp53<sup>C273X/C273X</sup></i> 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.
ISSN:2072-6694