Cancer results from the accumulated effects of somatic or inherited gene alterations that result in the improper function of proteins. An increased understanding of the underlying genetics has shaped the modern hypotheses for the basis of cancer. First was the concept of oncogenes, defined as genes that promote a transformed cellular phenotype. The altered activities of this class of proteins are usually due to mutations in the genes themselves, polymorphisms in promoter elements, or aberrant activation of upstream signaling pathways. The next concept with profound implications for the genetic basis of cancer was the discovery of tumor suppressor genes. This class of genes, when genetically silent, essentially takes the brakes off the normal controls of cell cycle, senescence, and apoptosis. From the silencing of genes in cancer emerged the rapidly growing field of epigenetics and how gene silencing leads to the development of cancer. Therefore, for the past several decades of molecular biology, the focus has been on the ON and OFF switching of genes. Engineering of recombinant DNA in model cell systems produced a greater understanding of the underlying biochemistry and molecular biology of cancer. This led to the belief that similar alterations could occur naturally in nearly any somatic cell type, and therefore cancer was believed to be of a stochastic nature.

The stochastic hypothesis suggests the clonal evolution model, in which any cell with overexpressed oncogenes and/or downregulated tumor suppressors will eventually form a tumor. This model could explain the multiple aspects of human disease and clinical observations.