PRC2在恶性周围神经鞘瘤发病及演进中的作用及其分子机制

the inactivation of PRC2 play an important role in the pathogenesis of malignant peripheral nerve sheath tumor (MPNST).EED and SUZ12 are the core components of multiple PRC2, their molecule  genetic  alteration is the main reason for the inactivation of PRC2. In our preliminary study ,we discovered the loss of SUZ12 and EED in 12 MPNST samples by whole-genome sequencing.Based on this ,the aim of this project is to use PCR-Sanger sequencing, real-time PCR, Western blot,immunoprecipitation;and the EED, SUZ12 and EZH2 overexpression and RNAi construct by lentivirus system;cell culture and Xenograft animal experiments to investigate molecule genetic of SUZ12 ,EED and the aberrations of EZH2, another core component of multiple PRC2. Thus,we will analyze functional change of PRC2 ,and investigate the clinical significance of dysfunctional multiple PRC2,downstream gene regulating transcription and the alter signaling pathways of loss-function of PRC2, and expounds the role of PRC2 in the pathogenesis and progress of malignant peripheral nerve sheath tumor and its associated molecular mechanism.

PRC2失活在恶性周围神经鞘瘤（malignant peripheral nerve sheath tumor，MPNST)的发病中起重要作用，PRC2的两个主要组成成分EED及SUZ12的分子遗传学改变是其失活的主要原因。本项目围绕前期研究中通过小样本恶性周围神经鞘瘤全基因组测序发现的EED和SUZ12的基因缺失，拟采用PCR-Sanger测序、荧光实时定量PCR、基因转染、细胞培养及移植瘤动物实验等遗传组学及分子生物学方法，分析MPNST中EED和SUZ12的分子遗传学及PRC2另外一个重要组分EZH2的异常，并分析由此引起的PRC2的功能改变， 探讨PRC2复合物功能异常在MPNST中的临床意义及PRC2功能缺失导致的下游基因转录调控及信号通路的改变，从而阐述PRC2在MPNST的发病及演进中的作用及可能的分子生物学机制。

PRC2失活在恶性周围神经鞘瘤（malignant peripheral nerve sheath tumor，MPNST)的发病中起重要作用，PRC2的两个主要组成成分EED及SUZ12的分子遗传学改变是其失活的主要原因。本项目围绕前期研究中通过小样本恶性周围神经鞘瘤全基因组测序发现的EED和SUZ12的基因缺失，拟采用PCR-Sanger测序、荧光实时定量PCR、基因转染、细胞培养及移植瘤动物实验等遗传组学及分子生物学方法，分析MPNST中EED和SUZ12的分子遗传学及PRC2另外一个重要组分EZH2的异常，并分析由此引起的PRC2的功能改变，探讨PRC2复合物功能异常在MPNST中的临床意义及PRC2功能缺失导致的下游基因转录调控及信号通路的改变，从而阐述PRC2在MPNST的发病及演进中的作用及可能的分子生物学机制。