Cancer Genetics and Epigenetics 2015, Vol.3, No.14, 1-5
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cell cycle (p14, p15, p16), cell apoptosis (DAPK), cell
adhesion (CDH1, CDH13), detoxification (GSTP1)
(Choi and Lee, 2013). Hypermethylation is not an
independent branch of epigenetic control. It is closely
related to other parts, such as methyl-binding proteins,
DNA methyltransferases and histone deacetylase.
In addition to hypermethylation of promoter of tumor
suppressor genes, there are a large number of
literature showed that the global and gene specific loss
of methylation have been observed in cancer. There is
now an important question that hypermethyla tion
of promoter region can inhibit the expression of genes,
and whether or not the low methylation of specific
pro-growth genes will increase their expression in
cancers. A lot of works focused on DNA
hypomethylation in cancer but unfortunately most of
them have not analyzed the relation between the
oncogenes expression level and their promoter region
hypomethylation. Because there are a large majority
of the cytosine located in repeated sequences, mainly
the transposons. The global hypomethylation induced
by repeated sequences demethylation in cancer has a
close relationship with the mutation and genome
instability (Easwaran and Baylin, 2013). We
will discuss this issue in detail later.
We can see a great difference in the pattern of methylation
in cancer and normal tissues. Differentially methylated
regions (DMRs) play critical roles in development,
aging and diseases. With the development of the next
generation sequencing technology, the resolution of
human genome methylation spectrum will be
increasingly higher, but the price of sequencing will
decrease very fast. Advances in technology
have provided a great convenience for the study of the
difference methylation pattern between cancer and
normal tissues, but it has also brought a huge
challenge to the data analysis. As a result, more and
more highly effective and accurate bioinformatics
tools and methods have been developed. For example,
CpG_MPs: identification of CpG methylation patterns
of genomic regions from high-throughput bisulfite
sequencing data (Su et al., 2013); QDMR: a
quantitative method for identification of differentially
methylated regions by entropy (Zhang et al., 2011).
With so many people’s efforts, we believe that more
secrets hidden in DNA methylation will slowly be
revealed.
4 DNA Methylation and Genomic Instability
It is worth noting that global hypomethylation is
closely related to the genetic instability mentioned
above, which implies that the abnormal methylation
status in cancer cells plays an important role in the
process of chromosome deviation.
A lot of studies have confirmed that global DNA
hypomethylation can increase the instability of the
chromosome and is very important in cancer. The
methylation status of the long interspersed nuclear
element-1 (LINE-1) sequence is a marker of global
methylation. The methylation level of LINE-1 is lower
than that of normal mucosa and is significantly
correlated with lymph node metastasis, and the
frequency of p53 mutation in esophageal squamous
carcinoma cells (Kawano et al., 2014). Hiroyuki
Kawano and coworkers point out that the whole
genome hypomethylation caused by chronic
inflammation, which initiate carcinogenesis of
esophageal squamous cell carcinoma through
chromosome instability. In addition, another team has
been investigated the relationship between LINE-1
hypomethylation and chromosome abnormalities in
the gastrointestinal stromal tumor (GISTs) (Igarashi et
al., 2010). By carrying out an array CGH analysis they
wanted to know whether LINE-1 hypomethylation is
linked with chromosomal gain or loss. The results
showed that chromosomal abnormalities associated
with LINE-1 hypomethylation are often represented as
losses, not gains and suggested a significant
relationship between LINE-1 hypomethylation and
DNA copy number variation in GISTs. Cristian
Coarfa’s group have developed several tools such as
Breakout, an algorithm for fast and accurate detection
of structural variants, to investigate the interaction
between hypomethylation and structural genomic
variants. They demonstrated some previous findings
that hypomehlation of DNA and binding sites of
Suz12 are closely associated with genome instability
in human germline. Their results suggested that structural
mutations are not randomly distributed relative to the
epigenome and are af4fected by the cell-type specific
hypomethylation patterns in both somatic cells and
germline.
The veil of hypomethylation affecting human genome
stability has been revealed. With the development of
the sequencing technology and analysis methods and
