Species And Cell Type Independent Core Myc Target Genes In Cancer And Stem Cells

The c-Myc (hereafter Myc) transcription factor augments the induction of pluripotency of somatic cells and contributes to human tumorigenesis, but the mechanisms by which Myc mediates these phenotypes remain only partially understood. To decipher Myc9s biological functions, it is essential to define its target genes. To date, numerous Myc target gene lists have been constructed in various cellular contexts from several species but no study has rigorously defined species and cell type independent core Myc targets. Using a model of human B lymphoma cells bearing inducible MYC, we identified direct Myc target genes via chromatin immunoprecipitation (ChIP), global nuclear run-on assay, and changes in mRNA levels. We also identified, for the first time, direct Myc targets in human embryonic stem cells (ESCs). Here we report that Myc regulates a core set of target genes that are shared in mouse and human ESCs as well as in four other human cancer cell types. The expression of this gene set is increased in Myc-expressing premalignant B lymphocytes and is highly elevated in lymphoma cells from Eμ-Myc transgenic mice. Remarkably, the expression of the core gene set significantly correlates with MYC expression across 8,129 microarray samples in Gene Expression Omnibus (GEO), which represent 312 cell and tissue types. Expression profiles of B cell lymphomas, acute leukemia, lung cancers and Ewing sarcomas are among those with the highest correlation. Annotation of this gene signature highlights Myc9s primordial function in ribosomal biogenesis as one of its key roles in cancer and stem cells. 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 928. doi:10.1158/1538-7445.AM2011-928