Cross Species Genomic Analysis Identifies a Mouse Model as Undifferentiated Pleomorphic Sarcoma/Malignant Fibrous Histiocytoma
Cross Species Genomic Analysis Identifies a Mouse Model as Undifferentiated Pleomorphic Sarcoma/Malignant Fibrous Histiocytoma
复制标题
DOI：
10.1371/journal.pone.0008075
复制
发表时间：
2009-11-30
期刊：
影响因子：
3.7
通讯作者：
Kirsch, David G.
中科院分区：
文献类型：
--
作者：
Mito, Jeffrey K.;Riedel, Richard F.;Kirsch, David G.
未分化多形性肉瘤/恶性纤维组织细胞瘤（MFH）是人类软组织肉瘤最常见的亚型之一。使用跨物种基因组分析，我们从LSL-Kras（G12 D）; Trp 53（Flox/Flox）软组织肉瘤小鼠模型中定义了一个高度富集人MFH的基因组。用这种小鼠基因组作为筛选器，我们鉴定了RAS靶FOXM 1在人MFH中的表达。Foxm 1的表达在转移到肺的小鼠肉瘤中升高，人MFH的组织芯片分析将FOXM 1的过表达与转移相关联。这些结果表明，存在于人MFH中的基因组改变在软组织肉瘤的LSL-Kras（G12 D）; p53（Flox/Flox）小鼠模型中是保守的，并证明了这种临床前模型的实用性。
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.