Functional genomics of cancer.

Cancer genomics has focused on the discovery of genetic mutations and chromosomal structural rearrangements that either increase susceptibility to cancer or support the cancer phenotype. Though each individual mutation may induce specific cancer phenotypes, it is the interaction of the functional changes in transcription and proteins that give the characteristics of cancer. Whereas molecular biology focuses on the impact of individual genes on the cancer state, functional genomics assesses the comprehensive genetic alterations in a cancer cell and seeks to integrate the dynamic changes in these networks so that cancer phenotypes can be explained. Most commonly, the transcriptome is the target of analysis because of the maturity, completeness, and speed of the technologies, but progressively the proteome is being studied in the same comprehensive manner. The focus of this review, however, will be on the functional consequences of cancer genomic alterations with special reference to the transcriptome and in the perturbed gene expression found in cancer states. The developments in the past two years (which is our time horizon) have been heavily driven by the applications of the new ultra high-throughput sequencing approaches assisted by computational discovery strategies. The precision and comprehensiveness of the analyses are astonishing. The collective results, when taken together, suggest that despite the large range of mutational and epigenetic events, there is a convergence onto a finite number of pathways that drive cancer behavior. Moreover, the interconnectivity of regulatory control mechanisms suggest that the earlier concepts distinguishing driver from passenger abnormalities may undervalue the contribution of the numerous aberrations that have small but additive effects on cancer virulence.