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  • Gene expression profiling is a powerful new approach for viewing the expression of many genes simultaneously in different types of malignant or normal cells. Using computational approaches, differentially expressed genes or informative patterns of expressed genes are mined from large data sets produced by new expression profiling technology. This technology yields the opportunity to classify tumors by gene expression and to locate genes of diagnostic or therapeutic importance.

  • DNA array technology uses thousands of DNA fragments arrayed on a solid surface in order to probe many messenger ribonucleic acid (mRNA) levels in one experiment. Both oligonucleotides and portions of complementary deoxyribonucleic acid (cDNA) are used as hybridization probes on the arrays. Clustering and other statistical based algorithms are used to locate patterns of gene expression of importance when analyzing large numbers of RNA samples.

  • Serial Analysis of Gene Expression (SAGE) is a sequencing based technology that provides an in-depth quantitative assessment of gene expression. SAGE works by counting transcripts and storing digital values electronically, providing absolute gene expression levels that make historical comparisons and databasing facile. It is useful for studying small numbers of tissue or cellular samples derived from well-controlled experiments.

  • Gene expression profiling techniques have been used to obtain global gene expression patterns from several common malignancies and corresponding normal tissues. These studies highlight the potential of gene expression profiling in cancer taxonomy, and in the identification of molecular targets for diagnosis and therapy.

  • Gene expression profiling has been used in the dissection of specific oncogenic molecular pathways, including the p53 tumor-suppressor pathway, the APC/β-catenin pathway, and numerous in vitro and in vivo models of angiogenesis and cancer drug resistance.


The ability to determine gene expression levels from thousands of genes simultaneously has recently transformed many aspects of cancer research. Large-scale gene expression profiling provides a powerful means to create an overall view of how the genome provides instructions to the cell. Ultimately, the genetic background, mutations, environment, and history of the cell all impact on mRNA and subsequent protein expression. Unlike the positional-cloning approaches that during the last decade revealed the genes mutated during oncogenesis, gene expression profiling does not directly reveal cancer-causing genes, but the pattern of genes used by the malignant (or normal) cell. These patterns, and the differentially expressed genes found within these patterns, have a variety of important uses for improved clinical correlation or therapy design. This chapter reviews the major mRNA profiling techniques and how they are applied to the study of cancer.

Technology advances make research advances possible. Just as the invention of the first compound microscope allowed biologists to view cellular patterns in tissues, the recent advent of gene expression technologies allows the biologist to observe molecular patterns in cells. Although protein levels are the ultimate goal for many uses, large numbers of protein levels cannot be assayed as rapidly as RNA, and this chapter is mostly limited to ...

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