滑膜肉瘤的条件性小鼠模型：对肌源性起源的见解

A conditional mouse model of synovial sarcoma: insights into a myogenic origin.

作者信息

Haldar Malay, Hancock Jeffrey D, Coffin Cheryl M, Lessnick Stephen L, Capecchi Mario R

机构信息

Department of Human Genetics, The Center for Children, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.

出版信息

Cancer Cell. 2007 Apr;11(4):375-88. doi: 10.1016/j.ccr.2007.01.016.

DOI:10.1016/j.ccr.2007.01.016

PMID:17418413

Abstract

Synovial sarcoma is an aggressive soft-tissue malignancy marked by a unique t(X;18) translocation leading to expression of a chimeric SYT-SSX fusion protein. We report here a mouse model of synovial sarcoma based on conditional expression of the human SYT-SSX2. Using this model, we have identified myoblasts as a potential source of synovial sarcoma. Remarkably, within the skeletal muscle lineage, while expression of the oncoprotein in immature myoblasts leads to induction of synovial sarcoma with 100% penetrance, its expression in more differentiated cells induces myopathy without tumor induction. We also show that early widespread expression of the fusion protein disrupts normal embryogenesis, causing lethality.

摘要

滑膜肉瘤是一种侵袭性软组织恶性肿瘤，其特征是独特的t(X;18)易位，导致嵌合性SYT-SSX融合蛋白的表达。我们在此报告一种基于人SYT-SSX2条件性表达的滑膜肉瘤小鼠模型。利用该模型，我们已确定成肌细胞是滑膜肉瘤的一个潜在来源。值得注意的是，在骨骼肌谱系中，虽然癌蛋白在未成熟成肌细胞中的表达导致滑膜肉瘤的诱导，发生率为100%，但其在分化程度更高的细胞中的表达诱导了肌病，而未诱导肿瘤。我们还表明，融合蛋白的早期广泛表达会破坏正常胚胎发育，导致死亡。