DNA microarrays in pediatric cancer

Childhood cancer, like all cancer, is at heart a genetic disease. Consequen tly, fundamental understanding of the oncogenic process is likely to be ben eficially addressed by genetic methodology. Current methods have largely fo cused on single-gene defects, like chimeric genes, which are present in man y sarcomas and leukemias. Real understanding is more likely to derive from a genome-wide analysis of these malignancies. Recent technologic advances h ave made it possible to simultaneously assess the entire expressed gene pro file, or transcriptome, of a given cancer. Foremost among these methods is gene expression profiling using DNA microarrays. Two basic approaches predo minate: spotted arrays and photolithography arrays. Regardless of the metho d, the resulting information can be used to create disease profiles, but on ly if appropriate bioinformatic solutions are employed. Common analytic app roaches include two-way expression comparisons, or scatter analyses; outlie r gene analysis, to identify significantly dysregulated genes; dendrogram a nalyses, as pioneered by Eisen; cluster analyses to identify diagnostic or biologic groups; and various forms of functional analyses to identify relev ant genes and biologic pathways. Studies of both adult and pediatric cancer have demonstrated the feasibility of such analyses to identify both diagno stic and prognostic groups of tumors. Acute childhood leukemias have been g rouped into myelogenous and lymphoid, and even B- and T-cell subsets, Breas t cancer prognostic groups have been identified on the basis of a small sub set of expressed genes. In addition, preliminary data on childhood sarcomas appear to identify both diagnostic and prognostic subsets, Specifically, e mbryonal rhabdomyosarcoma could be distinguished from alveolar rhabdomyosar coma, and even morphologically mixed embryonal and alveolar rhabdomyosarcom a showed similar gene expression profiles in both histologies. Further, col laborative studies using clustering analyses appear to identify prognostic groups of diverse sarcomas. Larger institutional and cooperative group stud ies are currently underway to validate these preliminary findings.