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

Duke University
University of Texas MD Anderson Cancer Center
Massachusetts General Hospital
Massachusetts Institute of Technology
Howard Hughes Medical Institute

Research output: Contribution to journal › Article › peer-review

63 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
Article number	e8075
Journal	PLoS ONE
Volume	4
Issue number	11
DOIs	https://doi.org/10.1371/journal.pone.0008075
State	Published - 27 Mar 2013
Externally published	Yes

Funding

Funders	Funder number
National Cancer Institute	R01CA138265

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1371/journal.pone.0008075

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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. (2013). Cross Species Genomic Analysis Identifies a Mouse Model as Undifferentiated Pleomorphic Sarcoma/Malignant Fibrous Histiocytoma. PLoS ONE, 4(11), Article e8075. https://doi.org/10.1371/journal.pone.0008075

@article{c541f89893134065a4f60a7211101bad,

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.\}",

year = "2013",

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doi = "10.1371/journal.pone.0008075",

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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 2013, 'Cross Species Genomic Analysis Identifies a Mouse Model as Undifferentiated Pleomorphic Sarcoma/Malignant Fibrous Histiocytoma', PLoS ONE, vol. 4, no. 11, e8075. https://doi.org/10.1371/journal.pone.0008075

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T1 - Cross Species Genomic Analysis Identifies a Mouse Model as Undifferentiated Pleomorphic Sarcoma/Malignant Fibrous Histiocytoma

AU - Mito, Jeffrey K.

AU - Riedel, Richard F.

AU - Dodd, Leslie

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.

PY - 2013/3/27

Y1 - 2013/3/27

N2 - 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.

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

Funding

UN SDGs

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