Aberrant DNA Methylation and Genome Instability and Mutation in Cancer

Abstract

In the process of normal cells transforming into cancer cells with the disruption control of epigenetic and genetic, they will gradually acquire the cancer Hallmarks. Epigenetic and genetic influence each other and closely cooperate to promoter oncogenic transformation in variety ways. It is clear that DNA methylation plays important roles in generation of mutation of tumor suppressor genes (TSGs) eventually lead to inactivation such as the probability of C mutation to T of the well-known TSGs p53 is high due to 5-methylcytosine residues is more prone to spontaneous deamination. The most common pattern of epigenetic control of tumor suppressor genes inactivation is hypermethylation of promoter region in cancers and the hypermethylation of CpG islands can also contribute to the increasing mutation rate of tumor suppressor genes such as CpG islands hypermethylation appeared to be tightly linked with the V600E mutation of the BRAF oncogene in colorectal cancer. Global hypomethylation is closely associated with chromosomal instability, which the methylation status of LINE-1 is a marker of global methylation, there is a significant relationship between LINE-1 hypomethylation and DNA copy number variation in the gastrointestinal stromal tumor. Aberrant DNA methylation is pervasive in cancer, which is similar to genomic instability and mutation.