PARENT SESSION
9:00 AM to 11:00 AM
Wednesday, April 24, 2002
Symposium 20
Bioinformatics
Room: Nevada 8-9-10
Chair: Amundson, Sally²²National Institutes of Health, Bethesda, MD
Speakers: Boguski, Mark⁴; Bourne, Philip⁵; Khan, Javed⁶; Amundson, Sally⁷⁴Rosetta Inpharmatics, Kirkland, WA⁵San Diego Supercomputer Center, UCSD, La Jolla, CA⁶National Institutes of Health, Gaithersburg, MD⁷National Institutes of Health, Bethesda, MD

(S20-4) Expression profiling and informatic analysis of radiation reponse.

Amundson, Sally^*,1, Bittner, Michael², Lee, R.¹, Koch-Paiz, Christine¹, Fornace, Albert¹, ¹ National Cancer Institute, Bethesda, MD² National Human Genome Research Institute, Bethesda, MD

ABSTRACT-
Changes in gene expression at the mRNA level are important in many of the cellular responses to ionizing radiation, such as G1 checkpoint activation and apoptosis. These responses are the culmination of many complex signal transduction pathways, and may differ depending on genetic background and cell or tissue type. For example, in the transcriptional response associated with radiation-induced apoptosis, induction of some genes is limited to p53 wild-type cells from tissue types with the ability to undergo rapid apoptosis after irradiation. In contrast, other genes are triggered after irradiation in cell lines undergoing rapid apoptosis regardless of p53 status. From this and other examples, it is apparent that the pattern of stress gene response is cell type specific in both primary and transformed lines. We are applying microarray analysis to profile the radiation response of approximately 7000 genes in a panel of more than 60 human tumor cell lines. We have also measured clonogenic survival and caspase activation as an indicator of apoptosis in these cell lines. Informatic analysis techniques such as hierarchical clustering and multi-dimensional scaling analysis are being applied to identify sets of genes whose radiation responses are associated with classical parameters of radiation survival, as well as apoptosis, p53 status, and other cellular parameters. Such studies should provide valuable mechanistic insight into the cellular response to ionizing radiation and the signal transduction mechanisms involved, possibly leading to the identification of new targets for modifying radiation therapy.

KEYWORDS: gene expression, p53, microarray