TRANSCRIPTOME 2002: From Functional Genomics to Systems
Using SAGE to Explore the Genome
Saurabh Saha, Alberto Bardelli, Kenneth W. Kinzler, & Bert Vogelstein, Johns Hopkins Medical Institutions, The Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD
With the recent completion of the draft human genome sequence, the SAGE method is now uniquely poised to provide a bridge between the transcriptome and the genome. New modifications to the SAGE method have permitted the analysis of gene expression in cell subpopulations or microanatomic structures, providing access to unexplored transcriptomes of normal and disease biology. To gain insights into the molecular basis for colorectal cancer, we have used SAGE to compare the global gene expression profile of metastatic colorectal cancers, primary cancers, benign colorectal tumors, normal colorectal epithelium, and endothelium from normal and tumor tissues. Genes differentially expressed in these tissues may be useful as diagnostic or therapeutic targets and provide insights into the pathogenesis of colorectal cancer. Among the genes identified, the PRL-3 protein tyrosine phosphatase gene was of particular interest as it was expressed at high levels in each of 50 cancer metastases studied but at lower levels in non-metastatic tumors and normal colorectal epithelium. In a subset of metastases examined, multiple copies of the PRL-3 gene were found within a small amplicon located at chromosome 8q24.3. These data suggest that the PRL-3 gene is important for colorectal cancer metastasis and provides a new therapeutic target for these intractable lesions.
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