Abstract A27: Altered Epigenetic Regulation of Homeobox Genes in Human Oral Squamous Cell Carcinoma Cells

It is estimated that 41,380 new patients will be diagnosed with cancer of the oral cavity and the pharynx and 7,890 will die of those diseases in 2013 in the United States alone. More than 90% of all oral cavity cancers are of the squamous cell carcinoma (SCC) type. We identified numerous homeobox genes as differentially expressed between non tumorigenic oral keratinocytes OKF6-TERT1R and tumorigenic SCC9 cells. Data from Oncomine, a cancer microarray database, suggest that homeobox (HOX) genes are also dysregulated in oral SCC patients. The activities of Polycomb repressive complexes (PRC), which cause epigenetic modifications, and retinoic acid (RA) signaling can control HOX gene transcription in stem cells. HOXB7, HOXC10, HOXC13, and HOXD8 transcripts are higher in SCC9 than in OKF6-TERT1R cells; using ChIP (chromatin immunoprecipitation) we detected the PRC2 protein SUZ12 and the epigenetic H3K27me3 mark on histone H3 at these genes in OKF6-TERT1R, but not in SCC9 cells. In contrast, IRX1, IRX4, SIX2, and TSHZ3 transcripts are lower in SCC9 than in OKF6-TERT1R cells. We detected SUZ12 and the H3K27me3 mark at these genes in SCC9, but not in OKF6-TERT1R cells. SUZ12 and H3K27me3 levels were not altered by RA at these HOX genes in SCC9 and OKF6-TERT1R cells. We conclude that altered activity of PRC2 is associated with dysregulation of homeobox gene expression in human SCC cells, and that this dysregulation potentially plays a role in the neoplastic transformation of oral keratinocytes. An exciting future direction would be the elucidation of the molecular mechanisms driving aberrant homeobox gene expression in transformed oral keratinocytes by assessing additional epigenetic histone and DNA modifications present at these genes. Such experiments are currently underway. Citation Format: Katarzyna M. Marcinkiewicz, Lorraine J. Gudas. Altered epigenetic regulation of homeobox genes in human oral squamous cell carcinoma cells. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Jun 19-22, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2013;73(13 Suppl):Abstract nr A27.