Rhodes Daniel R, Kalyana-Sundaram Shanker, Mahavisno Vasudeva, Barrette Terrence R, Ghosh Debashis, Chinnaiyan Arul M
Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Nat Genet. 2005 Jun;37(6):579-83. doi: 10.1038/ng1578.
DNA microarrays have been widely applied to cancer transcriptome analysis. The Oncomine database contains a large collection of such data, as well as hundreds of derived gene-expression signatures. We studied the regulatory mechanisms responsible for gene deregulation in these cancer signatures by searching for the coordinate regulation of genes with common transcription factor binding sites. We found that genes with binding sites for the archetypal cancer transcription factor, E2F, were disproportionately overexpressed in a wide variety of cancers, whereas genes with binding sites for other transcription factors, such as Myc-Max, c-Rel and ATF, were disproportionately overexpressed in specific cancer types. These results suggest that alterations in pathways activating these transcription factors may be responsible for the observed gene deregulation and cancer pathogenesis.
DNA微阵列已广泛应用于癌症转录组分析。Oncomine数据库包含大量此类数据以及数百个衍生的基因表达特征。我们通过寻找具有共同转录因子结合位点的基因的协同调控，研究了这些癌症特征中基因失调的调控机制。我们发现，具有典型癌症转录因子E2F结合位点的基因在多种癌症中过度表达的比例过高，而具有其他转录因子（如Myc-Max、c-Rel和ATF）结合位点的基因在特定癌症类型中过度表达的比例过高。这些结果表明，激活这些转录因子的信号通路改变可能是观察到的基因失调和癌症发病机制的原因。
