Microarrays and the Genetic Analysis of Brain Tumors

Cancer is the result of cumulative multiple genetic mutations, which result in the activation of oncogenes and / or the inactivation of tumor suppressor genes. Current theories of malignant transformation postulate that the development of primary brain tumors is the consequence of the sequential accumulation of multiple genetic alterations in brain cells, each of which contributes to the induction of a progressively more malignant phenotype. Traditionally, our understanding of brain tumor biology has come from the study of single specific genes or chromosome regions at a time. Although several genetic aberrations and gene expression changes have been identified using such focused techniques, the traditional methods of cancer research are tediously slow and provide limited insight into the global gene expression patterns that occur during the malignant transformation, development, and progression of primary brain cancers. Because hundreds of genes may be simultaneously involved in the mechanisms of carcinogenesis, new genomic high-throughput technologies have recently come into the forefront of cancer research. These technologies, which include cDNA and oligonucleotide microarrays (gene chips) and tissue microarray (tissue chip) techniques, may considerably facilitate the molecular profiling of human tumors. Such molecular fingerprinting of malignant gliomas, for example, may lead to advances in diagnosis, prognosis, and design of novel therapeutic approaches that could improve the clinical outcome of patients suffering from this rapidly fatal disease. This review will describe the principles of microarray technology as applied to human brain tumor research, summarize its use and limitations in identifying brain tumor-associated genes thus far, and speculate on the future applications and clinical ramifications of such genomic large-scale screening techniques in neuro-oncology.