Cancer Genetics and Epigenetics 2015, Vol.3, No.14, 1-5
1
Research Report Open Access
Aberrant DNA Methylation and Genome Instability and Mutation in Cancer
Li S., Wen Y.H., Wei Y.J., Wang Y.H., Liu H.B.
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China
Corresponding author email
Cancer Genetics and Epigenetics, 2015, Vol.3, No.14 doi: 10.5376/cge.2015.03.00014
Received: 2 Oct., 2015
Accepted: 13 Nov., 2015
Published: 20 Nov., 2015
© 2015 Li et al., This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use,
distribution, and reproduction in any medium, provided the original work is properly cited.
Preferred citation for this article:
Li S., Wen Y.H., Wei Y.J., Wang Y.H., and Liu H.B., 2015, Aberrant DNA methylation and genome instability and mutation in cancer, Vol.3, No.14, 1-5
(doi:
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.
Keywords
Hypermethylation; Hypomethylation; Chromosomal instability; Mutation; Cancer
1 Introduction
In the successful disruption of cell proliferation, and
angiogenesis, cell death, invasion and metastasis of
the control, the normal cells will gradually turn into
cancer cells (Hanahan and Weinberg, 2011). This
process of evolution is the need to continue to
accumulate carcinogenic characteristics in the clonal
cell line and most importantly genetic mechanisms
such as mutation, copy number variation, insertion,
deletion, and recombination are consistent with the
changes in the phenotype of the tumor. For this reason,
cancer is considered to be a genetic disease for a long
time (Choi and Lee, 2013; Esteller and Herman, 2002).
However, the probability of occurrence of these
genetic events is very low, so it is not a particularly
effective method for malignant tumors, the epigenetic
control mechanisms provide another option for
obtaining stable oncogenic characteristics. Epigenetic
states are flexible and varied in the process of cell
differentiation, but they are important in determining
the phenotype of cells. With the ongoing genetic and
epigenetic studies, we know that they will interact
with each other and work together to help the cells
acquire cancer Hallmarks.
DNAmethylation is a heritable but irreversible epigenetic
modification, which has the potential to change the
gene expression and has the profound development
and the genetic influence (Jones and Baylin, 2002).
Methylation can induce mutation, methylated cytosine
normally occurs the probability of mutation of 10 to
40 times higher compared with unmethylated (Jones
and Gonzalgo, 1997; Esteller and Herman, 2002;
Rideout et al., 1990). Methylation has a prominent
contribution to the generation of biological diversity
and the germ-line mutation and to transition mutation
which leads to tumor suppressor gene inactivation. In
addition to mutations, tumor suppressor gene can also
inactivated by high methylation level of promoter. The
change of DNA methylation is a common feature of
cancer and plays a driver role in the tumor primary
formation process, this view has been confirmed by a
lot of studies (Chen et al., 2015; Kok-Sin et al., 2015).
The roles of 5-methylcytosine in cancer is specifically
manifested in the following three aspects.
