Abstract
BackgroundDNA methylation is an epigenetic event involving the addition of a methyl-group to a cytosine-guanine base pair (i.e., CpG site). It is associated with different cancers. Our research focuses on studying non-small cell lung cancer hemimethylation, which refers to methylation occurring on only one of the two DNA strands. Many studies often assume that methylation occurs on both DNA strands at a CpG site. However, recent publications show the existence of hemimethylation and its significant impact. Therefore, it is important to identify cancer hemimethylation patterns.MethodsIn this paper, we use the Wilcoxon signed rank test to identify hemimethylated CpG sites based on publicly available non-small cell lung cancer methylation sequencing data. We then identify two types of hemimethylated CpG clusters, regular and polarity clusters, and genes with large numbers of hemimethylated sites. Highly hemimethylated genes are then studied for their biological interactions using available bioinformatics tools.ResultsIn this paper, we have conducted the first-ever investigation of hemimethylation in lung cancer. Our results show that hemimethylation does exist in lung cells either as singletons or clusters. Most clusters contain only two or three CpG sites. Polarity clusters are much shorter than regular clusters and appear less frequently. The majority of clusters found in tumor samples have no overlap with clusters found in normal samples, and vice versa. Several genes that are known to be associated with cancer are hemimethylated differently between the cancerous and normal samples. Furthermore, highly hemimethylated genes exhibit many different interactions with other genes that may be associated with cancer. Hemimethylation has diverse patterns and frequencies that are comparable between normal and tumorous cells. Therefore, hemimethylation may be related to both normal and tumor cell development.ConclusionsOur research has identified CpG clusters and genes that are hemimethylated in normal and lung tumor samples. Due to the potential impact of hemimethylation on gene expression and cell function, these clusters and genes may be important to advance our understanding of the development and progression of non-small cell lung cancer.
Highlights
DNA methylation is an epigenetic event involving the addition of a methyl-group to a cytosineguanine base pair (i.e., The shorthand notation for 5′-cytosine-phosphate-guanine-3′ (CpG) site)
Demethylation is the action of a methyl group being removed from a CpG site, and it can be observed in two forms: passive and active [6]
There are similar numbers of hemimethylation sites in tumor and normal samples, but the proportion in clusters is slightly higher in normal samples
Summary
DNA methylation is an epigenetic event involving the addition of a methyl-group to a cytosineguanine base pair (i.e., CpG site). Our research focuses on studying non-small cell lung cancer hemimethylation, which refers to methylation occurring on only one of the two DNA strands. In order to diagnose and treat lung cancer, it is important to identify genetic and epigenetic biomarkers. One important epigenetic biomarker or event is DNA methylation It is the covalent bonding of a methyl group (−CH3) to a CpG site in a mammalian cell; this is an epigenetic alteration to the DNA, meaning the DNA sequence does not change. Active demethylation is the deliberate removal of a methyl group from a CpG [7]
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