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Peripheral position of CCND1 and HER-2eu oncogenes within chromosome territories in esophageal and gastric cancers non-related to amplification and overexpression

机译:与扩增和过表达无关的食管和胃癌染色体区域内CCND1和HER-2 / neu癌基因的周围位置

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摘要

Interphase chromosomes have been shown to occupy discrete regions of the nucleus denominated chromosome territories (CTs), their active genes being preferentially positioned on the surfaces of these CTs, where they are accessible to transcriptional machinery. By means of FISH (Fluorescence in situ Hybridization), we analyzed the CCND1 and HER-2eu gene positions within the CTs and their relationship with gene amplification and protein over-expression in esophageal and gastric cancers. The CCND1 and HER-2/Neu genes were more often positioned at the periphery (mean frequency of 60%-83%) of the CTs in tumor tissues of the esophagus and stomach. Moreover, this positioning revealed no association with either gene amplification or the protein over-expression status of these genes, although, in esophageal carcinoma, Kappa statistics showed a moderate agreement between amplification of the CCND1 gene (Kappa = 0.400) and its location within the CT, as well as with over-expression of the corresponding protein (Kappa = 0.444). Thus, our results suggest that gene positioning in interphase chromosomes does not follow a definitive pattern neither does it depend only on gene transcriptional activity. Apparently, this positioning could be both gene- and tissue-specific, and depends on other factors acting together, such as dense-gene, chromosome size, chromatin structure, and the level and stability of its expression.
机译:已显示相间染色体占据了以核命名的染色体领地(CT)的离散区域,它们的活性基因优先位于这些CT的表面上,在这些表面上它们可被转录机器访问。通过FISH(荧光原位杂交),我们分析了食管癌和胃癌中CT的CCND1和HER-2 / neu基因位置及其与基因扩增和蛋白质过表达的关系。 CCND1和HER-2 / Neu基因更常位于食管和胃的肿瘤组织中CT的外围(平均频率为60%-83%)。此外,尽管在食管癌中,Kappa统计数据显示CCND1基因的扩增(Kappa = 0.400)与其在胃癌中的位置之间存在适度的一致性,但这种定位没有显示与这些基因的基因扩增或蛋白质过表达状态相关。 CT以及相应蛋白的过表达(Kappa = 0.444)。因此,我们的结果表明,相间染色体中的基因定位不遵循确定的模式,也不仅仅取决于基因的转录活性。显然,这种定位既可以是基因特异性的,也可以是组织特异性的,并且取决于其他因素共同作用,例如致密基因,染色体大小,染色质结构及其表达的水平和稳定性。

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