Identification of the genes involved in the tumorigenesis and spontaneous regression of neuroblastoma via array CGH analysis with model mice

我们试图通过MYCN Tg小鼠（一种神经母细胞瘤模型）的阵列CGH分析来确定参与神经母细胞瘤发生和自发消退的基因。为了评估染色体畸变的巨大数量，我们设置了三个参数并计算了分数。结果，我们确定了在所有12个晚期肿瘤中缺失的基因Cited2。从Cited2的表达水平来看，MYCN Tg小鼠的神经母细胞瘤由两个可区分的群体组成。低表达的细胞比高表达的细胞具有更高的致瘤能力。我们还发现Cited2影响其他神经母细胞瘤相关转录因子的表达。此外，虽然低表达的细胞在体内会产生高表达，但相反的情况从未发生。这一结果表明，低层次的人优于高层次的人。综上所述，Cited2的低表达可能是神经母细胞瘤肿瘤干细胞的标志。

We tried to identify the genes involved in the tumorigenesis and spontaneous regression of neuroblastoma via array CGH analysis with MYCN Tg mice, a model for neuroblastoma. For the purpose of evaluating the huge number of chromosomal aberrations, we set three parameters and calculated the scores. As a result, we identified the gene, Cited2, which is deleted in all 12 terminal tumors. Neuroblastoma in MYCN Tg mice turned out to be composed of two distinguishable populations in terms of the expression level of Cited2. The cells with low Cited2 expression showed strikingly higher tumorigenic ability compared to high ones. We also found that Cited2 affected the expression of other neuroblastoma-related transcription factors. In addition, although the cells with low Cited2 expression gave rise to high ones in vivo, the opposite never occurred. This result indicates the hierarchy that the low ones are superior to high ones. Taken together, the low expression of Cited2 might be the hallmark as cancer stem cells of neuroblastoma.