PLoS ONE (Nov 2009)

Cross species genomic analysis identifies a mouse model as undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma.

  • Jeffrey K Mito,
  • Richard F Riedel,
  • Leslie Dodd,
  • Guy Lahat,
  • Alexander J Lazar,
  • Rebecca D Dodd,
  • Lars Stangenberg,
  • William C Eward,
  • Francis J Hornicek,
  • Sam S Yoon,
  • Brian E Brigman,
  • Tyler Jacks,
  • Dina Lev,
  • Sayan Mukherjee,
  • David G Kirsch

DOI
https://doi.org/10.1371/journal.pone.0008075
Journal volume & issue
Vol. 4, no. 11
p. e8075

Abstract

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Undifferentiated pleomorphic sarcoma/Malignant Fibrous Histiocytoma (MFH) is one of the most common subtypes of human soft tissue sarcoma. Using cross species genomic analysis, we define a geneset from the LSL-Kras(G12D); Trp53(Flox/Flox) mouse model of soft tissue sarcoma that is highly enriched in human MFH. With this mouse geneset as a filter, we identify expression of the RAS target FOXM1 in human MFH. Expression of Foxm1 is elevated in mouse sarcomas that metastasize to the lung and tissue microarray analysis of human MFH correlates overexpression of FOXM1 with metastasis. These results suggest that genomic alterations present in human MFH are conserved in the LSL-Kras(G12D); p53(Flox/Flox) mouse model of soft tissue sarcoma and demonstrate the utility of this pre-clinical model.