Radio-responsive gene expression followed by alterations of DNA methylation status in cancer cell lines

[Objectives] DNA methylation is one of the epigenetic modifications that occurs in genome of mammals to ensure the proper regulation of gene expression in response to environmental stimuli. However, the regulation of gene expression by DNA methylation after genotoxic stress including irradiation remains poorly understood.We hypothesized that irradiation may elicit alterations in the methylation status of DNA and subsequently alter gene expression.[Methods] We have attempted to integrate the result of comprehensive gene expression analysis and DNA methylation analysis in response to irradiation in cell lines derived from human pancreatic cancer. Gene expression in these cell lines at 48 h after irradiation with X-ray at 4 Gy, or a carbon ion beam at 2 Gy were analyzed by microarray. DNA methylation status in the cell lines in these conditions were analyzed by new generation sequencing.[Results] In total, expression of 62 genes or 226 genes were changed by X-ray or carbon ion beam irradiation. 45 genes (73 %) of the 62 genes altered DNA methylation status while 186 genes (82 %) of 226 genes altered DNA methylation status by the irradiation. Expressions of some radio-responsive genes were also measured in the cells treated with 5-aza-2\u27-deoxycytidine reagent. Expressions of these radio-responsive genes were cell line specific, whereas expression of 38 genes responded to both X-ray and carbon ion beam irradiation.[Conclusions] Our study revealed that irradiated cells changed their gene expression followed by alteration of neighboring DNA methylation status. These data supports that NGS is powerful tool to analyze methylation status of human genomes.The 2nd Japan-China Symposium on Cancer Researc