Integrated analysis of genetic and epigenetic alterations in cancer

A proposed genetic model describing the transition from normal colonic epithelium to malignant cancer involves mutation of a number of key oncogenes and tumor suppressor genes. However, only subsets of colorectal cancers contain such mutations. Moreover, the heterogeneous pattern of tumor mutations suggests there are multiple alternative pathways leading to colonic tumorigenesis. These alternative pathways involve epigenetic alterations such as the methylation of multiple CpG islands, termed the CpG island methylator phenotype, and cancers with CpG island methylator phenotype show distinct genetic and clinicopathological features. The causes of these epigenetic alterations are still not fully understood, but exogenous pathogens such as Helicobacter pylori and Epstein-Barr virus, and the chromosomal translocations seen in leukemia, have all been shown to induce epigenetic alterations of genes.