Abstract 1813: FOXM1 target genes associated with cell cycle regulation predict breast cancer metastatic outcome.

FOXM1 is a key transcription factor regulating both cell proliferation and DNA damage checkpoint responses; and previous studies have demonstrated that higher breast cancer FOXM1 expression is associated with worse patient survival. Despite its functional and prognostic significance, the FOXM1 cistrome remains largely uncharacterized. Thus, in this study we utilized chromatin immune-precipitation sequencing (CHIPseq, GenPathway) and paired-end RNA-sequencing (RNAseq, UCSC) to comprehensively characterize the direct FOXM1 target genes associated with transcriptomic differences between actively proliferating and non-proliferating (confluent) ER+ MCF-7 cells. CHIPseq analysis identified ∼2.5K peaks with differential FOXM1 binding (MACS, p − 7 ). Peaks located within 5kb (-4.5kb to +0.5kb) of a transcription start site were assigned to genes, yielding 429 differentially bound genes. ∼5.1K genes were found to be differentially expressed (DESeq, BH-FDR corrected p 1.5). Of these, 145 were differentially bound by FOXM1 and referred to as direct target genes. These direct targets were enriched in 43 functional categories (GO biological processes, KEGG, Reactome or BioCarta pathways; Benjamini-corrected EASE score Citation Format: Christina Yau, Laurence Meyer, Stephen Benz, Charles Vaske, Gary Scott, Brian Egan, Paul Labhart, Elizabeth Mitchell, Nader Pourmand, Christopher Benz. FOXM1 target genes associated with cell cycle regulation predict breast cancer metastatic outcome. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1813. doi:10.1158/1538-7445.AM2013-1813