) The goal of this research is to use a first-generation DNA microarray system developed at Stanford to study gene expression patterns in normal and neoplastic human tissues. Rapidly growing knowledge of human expressed gene sequences will be applied to the problem of cancer by following the expression (at the mRNA level) of 10 to 20 thousand genes at once. Microarray hybridization will be used to study expression in a series of 60 human cancer cell lines already under intensive study by the NCI in connection with drug-susceptibility screening. Experience with these cell lines will aid in the design of experiments dealing with expression in samples of tumors and normal tissues provided by clinical collaborators. Arrangements have been made to obtain a large number of normal tissue samples from the genome anatomy project at NCI. Arrangements have also been made with clinical collaborators for preliminary surveys (ca. 100 samples) of lymphoma, breast cancer, colon cancer and leukemia. Suitably analyzed aggregate gene expression data should provide examples of genes whose expression, individually or as part of a complex pattern, is characteristic of particular types or sub-types of cancer. Information systems for acquisition, analysis and database storage of expression data will he put in place so that correlations of gene expression pattern with growth, physiology, disease state, drug susceptibility and eventually treatment outcome can be made. Mathematical algorithms for manipulating large datasets and testing similarity of expression patterns for many thousands of genes will be adapted or developed as needed.
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