Abstract 3074: Identification of a predominant pattern of co-regulation among kinetochore genes; prospective regulatory elements, and association with genomic instability

Abstract

Abstract The NCI-60 cell line panel is the most extensively characterized set of cells in existence. It provides multiple forms of data on different cancer types, and has been used extensively as a screening tool for drug discovery. Previously, the potential of this panel has not been applied to the fundamental cellular processes of chromosome segregation. In the current study, we used data from multiple microarray platforms accumulated for the NCI-60 to characterize an expression pattern of genes involved in kinetochore assembly. This analysis revealed that 17 genes encoding the constitutive centromere associated network of the kinetochore core (the CCAN complex) plus four additional genes with established importance in kinetochore maintenance (CENPE, CENPF, INCENP, and MIS12) exhibit similar patterns of expression in the NCI-60, suggesting a mechanism for co-regulated transcription of these genes which is maintained despite the multiple genetic and epigenetic rearrangements accumulated in these cells (such as variations in DNA copy number and karyotypic complexity). Several potential regulatory influences are identified for these genes, including transcription factors and microRNAs. Thus, our results provide a template for experimental studies on regulation of genes encoding kinetochore proteins, the process that, when aberrant, leads to the aneuploidy that is a hallmark of many cancers. We propose that the comparison of expression profiles in the NCI-60 cell line panel could be a tool for the identification of other genes groups whose products are involved in the assembly of organelle protein complexes. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3074. doi:10.1158/1538-7445.AM2011-3074