Identification of the 12q15 Amplicon within the Homogeneously Staining Regions in the Embryonal Rhabdomyosarcoma Cell Line RMS-YM
Identification of the 12q15 Amplicon within the Homogeneously Staining Regions in the Embryonal Rhabdomyosarcoma Cell Line RMS-YM
复制标题
胚胎横纹肌肉瘤细胞系 RMS-YM 均质染色区域内 12q15 扩增子的鉴定
DOI：
10.1159/000357930
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发表时间：
2014
影响因子：
1.7
通讯作者：
Hosoi H
中科院分区：
文献类型：
--
作者：
Kakazu N;Yamane H;Miyachi M;Shiwaku K;Hosoi H
基因扩增是多种肿瘤中癌基因过度表达的分子机制之一。均质染色区域(HSR)是基因扩增的细胞遗传学特征。横纹肌肉瘤是儿童最常见的恶性软组织肿瘤。RMS-YM是一个具有3个HSR的胚胎期横纹肌肉瘤细胞系。这一细胞遗传学发现提示在RMS-YM中存在与肿瘤发生或进展相关的基因扩增。在这里，使用荧光原位杂交，我们检测到MDM2基因在RMS-YM的HSR中高度扩增。我们还对扩增片段进行了精炼，证实了FRS2等基因在RMS-ym中得到了扩增。MDM2和FRS2分别作为p53的调节因子和成纤维细胞生长因子信号的介导者发挥重要作用，是许多不同肿瘤治疗的潜在分子靶点。RMS-YM可用于横纹肌肉瘤肿瘤发生和肿瘤进展的分子途径的研究，以及针对MDM2或FRS2的新开发的治疗药物的体外评估。
Gene amplification represents one of the molecular mechanisms of oncogene overexpression in many types of tumors. Homogeneously staining regions (HSRs) are cytogenetic hallmarks of gene amplification. Rhabdomyosarcoma is the most common malignant soft-tissue tumor in children. RMS-YM is an embryonal rhabdomyosarcoma cell line that possesses 3 HSRs. This cytogenetic finding suggests the presence of gene amplifications associated with tumor development or progression in RMS-YM. Here, using fluorescence in situ hybridization, we detected high amplification of the MDM2 gene in the HSRs of RMS-YM. We also refined the region of the amplicon and identified that the FRS2 gene and others are amplified in RMS-YM. MDM2 and FRS2 play important roles as a regulator of p53 and a mediator of FGF signaling, respectively, and thus are potential molecular targets for therapy in many different tumors. RMS-YM may be useful for studies of the molecular pathways of tumorigenesis and tumor progression in rhabdomyosarcoma and for in vitro evaluation of newly developed therapeutic agents that target MDM2 or FRS2.