Abstract
Aberrant DNA methylation is an important mechanism by which the normal patterns of microRNA expression are disrupted in human cancers including B-cell precursor acute lymphoblastic leukemia (BCP ALL), the most common pediatric malignancy. To characterize the methylation profile landscape of microRNA genes in BCP ALL patients. We employed Infinium® MethylationEPIC BeadChip Arrays to measure the methylation of microRNA genes from bone marrow samples of children with BCP ALL (n = 38) and controls without neoplasms (n = 4). This analysis revealed differential methylation of the microRNA genes in the pediatric BCP ALL when compared to the control. A subcluster amongst BCP ALL patients with TCF3-PBX1 genetic subtype was also observed. No other differences were observed in association with age, gender or risk group. Several interesting leukemia-related phenotypes are enriched by the genes with hyperand hypomethylated sites located in promoters as well as gene bodies. The top 3 miRNA genes, promoters of which were the most statistically significantly hypermethylated in BCP ALL were MIR1273G, MIR1304 and MIR663, and the top 3 hypomethylated were MIR4442, MIR155 and MIR3909. In this study, a different microRNA genes methylation landscape was shown in pediatric BCP ALL compared to children without neoplasms. A visible subcluster among BCP ALL samples consisted of individuals with TCF3-PBX1 genetic subtype. No other differences were observed in association with age, gender or risk group. Several interesting leukemia-connected phenotypes were found, associated with genes with hyperand hypomethylated sites located on promoters as well as gene bodies.
Highlights
Aberrant DNA methylation is an important mechanism by which the normal patterns of microRNA expression are disrupted in human cancers including B-cell precursor acute lymphoblastic leukemia (BCP ALL), the most common pediatric malignancy
This analysis revealed differential methylation of the microRNA genes in the pediatric BCP ALL when compared to the control
A different microRNA genes methylation landscape was shown in pediatric BCP ALL compared to children without neoplasms
Summary
Aberrant DNA methylation is an important mechanism by which the normal patterns of microRNA expression are disrupted in human cancers including B-cell precursor acute lymphoblastic leukemia (BCP ALL), the most common pediatric malignancy. Normal hematopoietic cell development is highly controlled epigenetic regulation of genes via DNA methylation, the chemical modification of histones, and the expression of noncoding RNAs. Normal hematopoietic cell development is highly controlled epigenetic regulation of genes via DNA methylation, the chemical modification of histones, and the expression of noncoding RNAs Each of these epigenetic factors can become dysregulated during leukemic transformation. The DNA methylation is by far the most well-characterized epigenetic modification and is involved in the regulation of gene expression, the maintenance of genome stability, and cellular differentiation.[2] The methylation of cytosine residues in CpG dinucleotides plays a pivotal role in the establishment of cellular identity by influencing gene expression.[3]
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