Gene discovery using the serial analysis of gene expression technique: Implications for cancer research

Cancer is a genetic disease. As such, our understanding of the pathobiology of tumors derives from analyses of the genes whose mutations are responsib le for those tumors. The cancer phenotype, however, likely reflects the cha nges in the expression patterns of hundreds or even thousands of genes that occur as a consequence of the primary mutation of an oncogene or a tumor s uppressor gene. Recently developed functional genomic approaches, such as D NA microarrays and serial analysis of gene expression (SAGE), have enabled researchers to determine the expression level of every gene in a given cell population, which represents that cell population's entire transcriptome, The most attractive feature of SAGE is its ability to evaluate the expressi on pattern of thousands of genes in a quantitative manner without prior seq uence information. This feature has been exploited in three extremely power ful applications of the technology: the definition of transcriptomes, the a nalysis of differences between the gene expression patterns of cancer cells and their normal counterparts, and the identification of downstream target s of oncogenes and tumor suppressor genes, Comprehensive analyses of gene e xpression not only will further understanding of growth regulatory pathways and the processes of tumorigenesis but also may identify new diagnostic an d prognostic markers as well as potential targets for therapeutic intervent ion. (C) 2001 by American Society of Clinical Oncology.