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To use a novel genomic approach to determine differential gene expression patterns in colon cancers of different metastatic potential.Colorectal cancer is the third leading cause of cancer deaths in the United States; despite aggressive treatment strategies, the 5-year survival rate for metastatic cancer has not changed in 50 years. The analysis of changes in gene expression patterns associated with metastasis may provide new treatment strategies.Human colon cancer cells KM12C (derived from a Dukes B colon cancer), KML4A (a metastatic variant derived from KM12C), and KM20 (derived from a Dukes D colon cancer) were extracted for RNA. In addition, RNA was extracted from normal colon, primary cancer, and liver metastasis in a patient with metastatic colon cancer. Gene expression patterns for approximately 1,200 human genes were analyzed and compared by cDNA array techniques.Of the roughly 1,200 genes assessed in the KM cell lines, 9 genes were noted to have a more than threefold change in expression (either increased or decreased) in the more metastatic KML4A and KM20 cells compared with KM12C. Assessment of tissues from a patient with metastatic colon cancer demonstrated a more than threefold change in the expression of 14 genes in the primary cancer and liver metastasis compared with normal mucosa.Using cDNA expression array technology, the authors identified genes with expression levels that are altered with metastasis. The ability to analyze and compare the expression patterns of multiple genes simultaneously provides a powerful technique to identify potential molecular targets for novel therapeutic strategies.