Chromosomal aneuploidy is a defining feature of epithelial cancers. The pattern of aneuploidies is cancer-type specific. For instance, the gain of chromosome 13 occurs almost exclusively in colorectal cancer. We used microcell-mediated chromosome transfer to generate gains of chromosome 13 in the diploid human colorectal cancer cell line DLD-1. Extra copies of chromosome 13 resulted in a significant and reproducible up-regulation of transcript levels of genes on chromosome 13 (P = .0004, FDR = 0.01) and a genome-wide transcriptional deregulation in all 8 independent clones generated. Genes contained in two clusters were particularly affected: the first cluster on cytoband 13q13 contained 7 highly up-regulated genes (NBEA, MAB21L1, DCLK1, SOHLH2, CCDC169, SPG20 and CCNA1, P = .0003) in all clones. A second cluster was located on 13q32.1 and contained five upregulated genes (ABCC4, CLDN10, DZIP1, DNAJC3 and UGGT2, P = .003). One gene, RASL11A, localized on chromosome band 13q12.2, escaped the copy number-induced overexpression and was reproducibly and significantly down-regulated on the mRNA and protein level (P = .0001, FDR = 0.002). RASL11A expression levels were also lower in primary colorectal tumors as compared to matched normal mucosa (P = .0001, FDR = 0.0001. Overexpression of RASL11A increases cell proliferation and anchorage independent growth while decreasing cell migration in +13 clones. In summary, we observed a strict correlation of genomic copy number and resident gene expression levels, and aneuploidy dependent consistent genome-wide transcriptional deregulation.

中文翻译：

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诱导的染色体非整倍性导致癌细胞转录组的整体和一致的失控。

染色体非整倍性是上皮癌的定义特征。非整倍性的模式是癌症类型特异性的。例如，第13号染色体的获得几乎仅在大肠癌中发生。我们使用微细胞介导的染色体转移在二倍体人结肠直肠癌细胞系DLD-1中产生13号染色体。13号染色体的额外副本导致13号染色体上的基因转录水平显着且可再现地上调（P = .0004，FDR = 0.01），并且在所有生成的8个独立克隆中，全基因组范围的转录失调。在两个簇中包含的基因受到了特别的影响：在细胞带13q13上的第一个簇在所有克隆中都包含7个高度上调的基因（NBEA，MAB21L1，DCLK1，SOHLH2，CCDC169，SPG20和CCNA1，P = .0003）。第二个群集位于13q32。1，并包含五个上调的基因（ABCC4，CLDN10，DZIP1，DNAJC3和UGGT2，P = 0.003）。一个位于染色体带13q12.2上的基因RASL11A逃脱了拷贝数诱导的过表达，并且在mRNA和蛋白质水平上可再现且显着下调（P = .0001，FDR = 0.002）。与匹配的正常粘膜相比，原发性结肠直肠肿瘤中的RASL11A表达水平也较低（P = .0001，FDR =0.0001。RASL11A的过表达增加了细胞增殖和锚定非依赖性生长，同时减少了+13个克隆中的细胞迁移。总而言之，我们观察到基因组拷贝数和驻留基因表达水平的严格相关性，以及非整倍体依赖性一致的全基因组转录调控。定位在染色体带13q12.2上，摆脱了拷贝数诱导的过表达，并且可重复且显着下调了mRNA和蛋白质水平（P = .0001，FDR = 0.002）。与匹配的正常粘膜相比，原发性结肠直肠肿瘤中的RASL11A表达水平也较低（P = .0001，FDR =0.0001。RASL11A的过表达增加了细胞增殖和锚定非依赖性生长，同时减少了+13个克隆中的细胞迁移。总而言之，我们观察到基因组拷贝数和驻留基因表达水平的严格相关性，以及非整倍体依赖性一致的全基因组转录调控。定位在染色体带13q12.2上，摆脱了拷贝数诱导的过表达，并且可重复且显着下调了mRNA和蛋白质水平（P = .0001，FDR = 0.002）。与匹配的正常粘膜相比，原发性结肠直肠肿瘤中的RASL11A表达水平也较低（P = .0001，FDR =0.0001。RASL11A的过表达增加了细胞增殖和锚定非依赖性生长，同时减少了+13个克隆中的细胞迁移。总而言之，我们观察到基因组拷贝数和驻留基因表达水平的严格相关性，以及非整倍体依赖性一致的全基因组转录调控。