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:10.1371/journal.pone.0008075

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

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60 Scopus citations

Abstract

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.

Original language	English (US)
Article number	e0008075
Journal	PloS one
Volume	4
Issue number	11
DOIs	https://doi.org/10.1371/journal.pone.0008075
State	Published - 2009

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology
General Agricultural and Biological Sciences
General

MD Anderson CCSG core facilities

Tissue Biospecimen and Pathology Resource

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Mito, J. K., Riedel, R. F., Dodd, L., Lahat, G., Lazar, A. J., Dodd, R. D., Stangenberg, L., Eward, W. C., Hornicek, F. J., Yoon, S. S., Brigman, B. E., Jacks, T., Lev, D., Mukherjee, S., & Kirsch, D. G. (2009). Cross Species Genomic Analysis Identifies a Mouse Model as Undifferentiated Pleomorphic Sarcoma/Malignant Fibrous Histiocytoma. PloS one, 4(11), Article e0008075. https://doi.org/10.1371/journal.pone.0008075

Mito, JK, Riedel, RF, Dodd, L, Lahat, G, Lazar, AJ, Dodd, RD, Stangenberg, L, Eward, WC, Hornicek, FJ, Yoon, SS, Brigman, BE, Jacks, T, Lev, D, Mukherjee, S & Kirsch, DG 2009, 'Cross Species Genomic Analysis Identifies a Mouse Model as Undifferentiated Pleomorphic Sarcoma/Malignant Fibrous Histiocytoma', PloS one, vol. 4, no. 11, e0008075. https://doi.org/10.1371/journal.pone.0008075

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title = "Cross Species Genomic Analysis Identifies a Mouse Model as Undifferentiated Pleomorphic Sarcoma/Malignant Fibrous Histiocytoma",

abstract = "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-KrasG12D; Trp53Flox/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-KrasG12D; p53Flox/Flox mouse model of soft tissue sarcoma and demonstrate the utility of this pre-clinical model.",

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

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AU - Lahat, Guy

AU - Lazar, Alexander J.

AU - Dodd, Rebecca D.

AU - Stangenberg, Lars

AU - Eward, William C.

AU - Hornicek, Francis J.

AU - Yoon, Sam S.

AU - Brigman, Brian E.

AU - Jacks, Tyler

AU - Lev, Dina

AU - Mukherjee, Sayan

AU - Kirsch, David G.

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AB - 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-KrasG12D; Trp53Flox/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-KrasG12D; p53Flox/Flox mouse model of soft tissue sarcoma and demonstrate the utility of this pre-clinical model.

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Cross Species Genomic Analysis Identifies a Mouse Model as Undifferentiated Pleomorphic Sarcoma/Malignant Fibrous Histiocytoma

Abstract

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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