Cross species genomic analysis identifies a mouse model as undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma.
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.
Mito
Jeffrey K
JK
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina, United States of America.
Riedel
Richard F
RF
Dodd
Leslie
L
Lahat
Guy
G
Lazar
Alexander J
AJ
Dodd
Rebecca D
RD
Stangenberg
Lars
L
Eward
William C
WC
Hornicek
Francis J
FJ
Yoon
Sam S
SS
Brigman
Brian E
BE
Jacks
Tyler
T
Lev
Dina
D
Mukherjee
Sayan
S
Kirsch
David G
DG
D000818:Animals; D004195:Disease Models, Animal; D020869:Gene Expression Profiling / Q000379:methods; D016158:Genes, p53; D016678:Genome; D023281:Genomics; D005838:Genotype; D051677:Histiocytoma, Malignant Fibrous / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D046228:Microarray Analysis; D009362:Neoplasm Metastasis; D012509:Sarcoma / Q000378:metabolism*; D012983:Soft Tissue Neoplasms / Q000378:metabolism; D013045:Species Specificity