Alternative splicing induced by ionizing radiation and transcriptional profiling of radiosensitive cancer patients

1460 We are characterizing the transcriptional response to ionizing radiation with particular interest in whole transcriptome alternative splicing. We have used human exon arrays to interrogate the genome for radiation-induced transcriptional expression products in human lymphoblastoid cell lines and primary fibroblasts at both the gene and exon levels. We have identified novel ionizing radiation-regulated gene expression products many of which have been validated by PCR-based techniques. In addition to quantitative changes of full length transcripts, identification of a large number of alternative splicing events were evident, many of which are previously uncharacterised, and that preferentially occur following ionizing radiation exposure. Likewise, we have conducted experiments to explore the transcriptional profile of radiation sensitive patients using these same cell types. We used cell lines from non-radiosensitive cancer patients as controls. We have identified gene expression profiles of radiosensitive patient cell lines and have identified alternative splicing products as well as gene expression differences that are unique to radiosensitive patient cell lines following treatment with ionizing radiation. We also are able to compare the transcriptional responses between these two cell types which will assist in exploring cell-type specific versus global responses. In conclusion, these results could lead to a better understanding of the radiation response and may enable the individualization of radiotherapy to optimize tumor control.