Gene expression profiling of lymphomas.
The functional phenotype of a cell results from the simultaneous action of many thousands of genes, which until recently could not be assessed using standard molecular biological techniques. Indeed, molecular genetics and cellular biology inadequately explain the molecular physiology of normal and diseased cells and provide a fragmented view of the role of various genes and their products. Recent advances in techniques of large-scale gene expression allow simultaneous study of thousands of genes of interest in a specific tissue/tumor of interest, and the ability to identify expression signatures associated with functional phenotypes. The application of gene expression profiling to lymphomas has already led to identification of distinct expression signatures associated with a germinal center cell and activated B-cell phenotype, and to the differentiation of tumor cells based on these stages of development. The differentiation of two stages of developmental arrest in large B-cell lymphomas suggests that this subtype is comprised of two diseases, albeit of similar histologic and immunophenotypic character, which were shown to have dramatically different outcomes following chemotherapy. Important information will also be obtained through the association of genes of unknown activity with functional cellular phenotypes and expression signatures, possibly leading to identification of new genes involved in lymphomagenesis and new targets for treatment.