Wu Z, Siadaty M S, Riddick G, Frierson H F, Lee J K, Golden W, Knuutila S, Hampton G M, El-Rifai W, Theodorescu D
Department of Molecular Physiology, Box 422, University of Virginia Health Sciences Center, Charlottesville, VA 22908, USA.
Neoplasia. 2006 Mar;8(3):181-9. doi: 10.1593/neo.05727.
Expression profiling by DNA microarray analysis has provided insights into molecular alterations that underpin cancer progression and metastasis. Although differential expression of microarray-defined probes can be related to numerical or structural chromosomal alterations, it is unclear if such changes are also clustered in distinct chromosomes or genomic regions and whether chromosomal alterations always reflect changes in gene expression. Here we apply the dChip algorithm and a novel technique to test the hypothesis that expression changes occurring as a function of tumor progression and metastasis are nonrandomly distributed. Expression profiling of a human xenograft model of lung metastasis phenotype indicates that chromosomes 2, 11, and 20 contain higher percentages of differentially expressed genes (P < .05). Furthermore, we show that a number of differentially expressed probes mapped to chromosome 17q, defining the existence of an expression "hot spot" corresponding to an area of gain determined by comparative genomic hybridization (CGH). Interestingly, other areas of gains detected by CGH were not associated with expression hot spots. In summary, we show that gene expression changes during bladder cancer lung metastasis occur nonrandomly in specific chromosomes and intrachromosomal locations.
通过DNA微阵列分析进行的表达谱分析为深入了解支撑癌症进展和转移的分子改变提供了线索。尽管微阵列定义探针的差异表达可能与染色体的数量或结构改变有关，但尚不清楚这些变化是否也聚集在不同的染色体或基因组区域，以及染色体改变是否总是反映基因表达的变化。在此，我们应用dChip算法和一种新技术来检验这样一个假设，即随着肿瘤进展和转移而发生的表达变化是非随机分布的。对具有肺转移表型的人异种移植模型进行表达谱分析表明，2号、11号和20号染色体含有较高比例的差异表达基因（P < 0.05）。此外，我们发现许多差异表达探针定位于17q染色体，这确定了一个与通过比较基因组杂交（CGH）确定的增益区域相对应的表达“热点”的存在。有趣的是，CGH检测到的其他增益区域与表达热点无关。总之，我们表明膀胱癌肺转移过程中的基因表达变化在特定染色体和染色体内位置非随机发生。
