The Epigenetic Component in Cancer Evolution

Cancerogenesis being an evolutionary process, the genotype × environment (G×E) concept can be applied to explain the cancer phenotype. In the current chapter I will first revisit and extend the initial notion of the G×E concept, and propose that G could be replaced by “inheritance system” in which heritability is a property of the system. The system is composed of at least two elements: the genotype and the epigenotype, that interact as a dual inheritance system with the environment, to bring about the phenotype. The elements of inheritance system are defined based on their molecular nature, that is, the DNA and the bearers of epigenetic information. Following the theoretical concept I will give an overview of the mechanisms underlying epigenetic variations: DNA methylation, histone modification, nuclear topography, and noncoding RNAs. Finally I will discuss the involvement of epigenetic variations in cancer development and progression. Current conceptual understanding accepts two nonmutually exclusive scenarios: one in which occurrence of epimutations is a very early step in cancerogenesis and drives the phenotype into mutations. The other scenario sees genotype and epigenotype to be interdependent. Whatever scenario holds true, including the epigenotype into the vision of cancer, evolution has profound effects on how diagnostic tools are developed and treatment is managed.