Department of Molecular Biology and Genetics, Boğaziçi University, Istanbul, Turkey.
Nucleic Acids Res. 2010 Nov;38(20):7008-21. doi: 10.1093/nar/gkq574. Epub 2010 Jul 9.
Cancer is among the major causes of human death and its mechanism(s) are not fully understood. We applied a novel meta-analysis approach to multiple sets of merged serial analysis of gene expression and microarray cancer data in order to analyze transcriptome alterations in human cancer. Our methodology, which we denote 'COgnate Gene Expression patterNing in tumours' (COGENT), unmasked numerous genes that were differentially expressed in multiple cancers. COGENT detected well-known tumor-associated (TA) genes such as TP53, EGFR and VEGF, as well as many multi-cancer, but not-yet-tumor-associated genes. In addition, we identified 81 co-regulated regions on the human genome (RIDGEs) by using expression data from all cancers. Some RIDGEs (28%) consist of paralog genes while another subset (30%) are specifically dysregulated in tumors but not in normal tissues. Furthermore, a significant number of RIDGEs are associated with GC-rich regions on the genome. All assembled data is freely available online (www.oncoreveal.org) as a tool implementing COGENT analysis of multi-cancer genes and RIDGEs. These findings engender a deeper understanding of cancer biology by demonstrating the existence of a pool of under-studied multi-cancer genes and by highlighting the cancer-specificity of some TA-RIDGEs.
癌症是人类死亡的主要原因之一，但其机制尚未完全阐明。我们应用了一种新的荟萃分析方法，对多组合并的基因表达序列分析和微阵列癌症数据进行分析，以研究人类癌症中的转录组变化。我们的方法被称为“肿瘤中同源基因表达模式分析”（COGENT），揭示了许多在多种癌症中差异表达的基因。COGENT 检测到了许多已知的肿瘤相关（TA）基因，如 TP53、EGFR 和 VEGF，以及许多多癌但尚未与肿瘤相关的基因。此外，我们还使用所有癌症的表达数据，鉴定了人类基因组上 81 个共调控区域（RIDGEs）。一些 RIDGEs（28%）由基因的同源基因组成，而另一部分（30%）则在肿瘤中特异性失调，而在正常组织中则没有。此外，相当数量的 RIDGEs与基因组上富含 GC 的区域相关。所有组装的数据都可以在网上免费获得（www.oncoreveal.org），作为一种工具，可以实现多癌基因和 RIDGEs 的 COGENT 分析。这些发现通过展示一组研究不足的多癌基因的存在，并强调一些 TA-RIDGEs 的肿瘤特异性，加深了对癌症生物学的理解。
