Cancer Genetics and Epigenetics 2015, Vol.3, No.11, 1-8
1
Research Article Open Access
The Aberrant Methylation Sites Identification and Function Analysis Associated
With DNMT3A And IDH Mutations in AML
Ci C., Wang Y.H., Gu Y., Su J.Z.
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China
Corresponding author email
Cancer Genetics and Epigenetics, 2015, Vol.3, No.11 doi: 10.5376/cge.2015.03.00011
Received: 17 Aug., 2015
Accepted: 18 Sep., 2015
Published: 30 Sep., 2015
© 2015 Ci 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:
Ci C., Wang Y.H., Gu Y.,and Su J.Z., 2015, The Aberrant Methylation Sites Identification and Function Analysis Associated With Dnmt3a And Idh Mutations
in Aml Cancer Genetics and Epigenetics, Vol.3, No.11, 1-8
Abstract
DNA methylation is a major epigenetic modification process. DNA methylation have played an important role in the
development of disease cells and normal cells. Mutations in the genetic sequence of DNMT3A and IDH are found in many patients
with acute myeloid leukemia. They lead to dysfunction of DNMT3A protein and isocitrate dehydrogenase and bad prognosis.
However, the process of how they regulate DNA methylation in acute myeloid leukemia, affecting the development of the disease is
not clear. Following work is conducted: In the analysis of survival, we have studied the influence of different mutations on patients’
survival, then we select DNMT3A and IDH genes as the key genes. We use JHU-USC HumanMethylation450K data of 74 AML
samples downloaded from The Cancer Genome Atlas
with 40 normal samples downloaded
from The Gene Expression Omnibus (
through QDMR
/)
and SAM(SAMR package is used to analyze significance of microarrays) method, 1,991 Differentially methylated sites(DMS) are
screened eventually, finally these CpG sites are mapped to 1,452 genes. Outcomes from cluster analysis illustrate that there exist little
differences in individuals from normal samples. Disease samples have a higher methylation proportion than normal samples. Then,
we match the genome for DMS and discover that the hypermethylation inclines to a lower expression in the promoter, DNA
methylation and gene expression in the sample indicate a slightly positive correlation on gene body. Functional enrichment analysis
illustrates that differentially methylated genes are mostly enriched in cancer pathway and cell adhesion. This topic is based on DNA
methylation to classify samples and do function analysis for DMS. It can provide the diagnosis and therapy of acute myeloid
leukemia with great help.
Keywords
Acute myeloid leukemia; DNA methylation; DNMT3A; IDH
Introduction
Acute myeloid leukemia (AML) contains all acute
non-lymphocytic leukemia. It is a highly heterogeneous
disease [1, 2].With improved treatments, the survival
rate and quality of life in patients with AML has
improved. Providing appropriate treatment plan by
disease risk grade and prognosis analysis of patients
is very important. AML is particularly common in
adults, the elderly people have higher disease
incidence than the young.
DNA methylation have an important role to induce the
disease and maintain cellular health lifecycle [3-5].
Individuals with acute myeloid leukemia (AML) tend
to suffer significant proportion
DNMT3A
and
IDH
mutations, which contributes to
DNMT3A
protein and
isocitrate dehydrogenase dysfunction and their poor
prognosis [6, 7].Firstly, we research the effect of
common mutations to patient survival and select
DNMT3A
,
IDH
gene as a key gene. Next, we use a
combination method of SAM and QDMR
(
) to screen DMS
and classify sample. Then, we analyze the relationship
between DNA methylation and gene expression of
different genomic regions. Finally, we do function
enrichment analysis for differentially methylated
genes. This topic is based on DNA methylation to
classify samples and do function analysis for DMS. It
can provide the diagnosis and therapy of acute myeloid
leukemia with great help.
The aim of the study is that identifying DMS between
disease samples and normal samples. Furthermore, we
explore that the function of DMS. Epigenetic
modifications do not change the gene sequence.
Epigenetic modification contains many classes, such
