In order to delineate targets for colon cancer treatment and chemoprevention, we use cDNA microarrays to determine the cellular pathways that are altered in neoplastic colon tissues. Microarrays involve the quantitative hybridization of a large panel of cloned genes or synthetic oligonucleotides with the cDNAs derived from a particular cell or tissue type. The overall hybridization to the microarray gives a comprehensive profile of the relative message levels for all genes represented in the microarray. We use these microarrays to determine the cellular pathways that are altered in neoplastic colon tissues. In a typical experiment, we obtain fresh normal, adenoma, and carcinoma tissue samples from surgically resected colons. We then isolate total RNA from each sample for comparison on microarrays. A striking feature of our colon tumor progression data is that many of the differentially expressed genes are lower in colon polyp and tumor tissues as compared to normal tissues. These observations have led us to focus our research programs on the function of the APC tumor suppressor gene and the role of DNA methylation in colon cancer development.