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跨物种基因组分析鉴定出一种作为未分化多形性肉瘤/恶性纤维组织细胞瘤的小鼠模型。

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

机构信息

Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina, United States of America.

出版信息

PLoS One. 2009 Nov 30;4(11):e8075. doi: 10.1371/journal.pone.0008075.

DOI:10.1371/journal.pone.0008075
PMID:19956606
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2779485/
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.

摘要

未分化多形性肉瘤/恶性纤维组织细胞瘤（MFH）是人类软组织肉瘤中最常见的亚型之一。通过跨物种基因组分析，我们从 LSL-Kras（G12D）；Trp53（Flox/Flox）软组织肉瘤小鼠模型中定义了一个基因集，该基因集在人类 MFH 中高度富集。利用这个小鼠基因集作为筛选器，我们在人类 MFH 中鉴定出了 RAS 靶基因 FOXM1 的表达。Foxm1 在转移到肺部的小鼠肉瘤中表达升高，并且人类 MFH 的组织微阵列分析表明 FOXM1 的过表达与转移相关。这些结果表明，存在于人类 MFH 中的基因组改变在 LSL-Kras（G12D）；p53（Flox/Flox）软组织肉瘤小鼠模型中是保守的，并证明了这个临床前模型的实用性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f76e/2779485/c20afd8eaa8e/pone.0008075.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f76e/2779485/34d06a8692c1/pone.0008075.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f76e/2779485/c20afd8eaa8e/pone.0008075.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f76e/2779485/34d06a8692c1/pone.0008075.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f76e/2779485/c20afd8eaa8e/pone.0008075.g002.jpg

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