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Comprehensive DNA Methylation Analysis Using a Methyl-CpG-binding Domain Capture-based Method in Chronic Lymphocytic Leukemia Patients
Published on: June 16, 2017
MicroRNA gene methylation landscape in pediatric B-cell precursor acute lymphoblastic leukemia
Radosław Chaber1,2, Artur Gurgul3, Jacek Tabarkiewicz1,4
1Institute of Medical Sciences, Medical College of Rzeszów University, Poland.
Background:
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.
Objectives:
To characterize the methylation profile landscape of microRNA genes in BCP ALL patients.
Material And Methods:
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).
Results:
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.
Conclusions:
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.
Insights
Aberrant DNA methylation disrupts microRNA expression in pediatric B-cell precursor acute lymphoblastic leukemia (BCP ALL). This study characterized the microRNA methylation landscape in BCP ALL, identifying specific methylation patterns and a TCF3-PBX1 genetic subtype subcluster.
Area of Science:
- Genomics and epigenetics
- Pediatric oncology
- Molecular biology
Background:
- Aberrant DNA methylation is a key mechanism disrupting microRNA (miRNA) expression in cancers.
- B-cell precursor acute lymphoblastic leukemia (BCP ALL) is the most common pediatric malignancy, with altered miRNA expression patterns.
- Understanding miRNA methylation is crucial for BCP ALL pathogenesis.
Purpose of the Study:
- To comprehensively characterize the microRNA gene methylation profile landscape in pediatric BCP ALL patients.
- To identify specific miRNA methylation signatures associated with BCP ALL.
- To explore potential correlations between methylation patterns and BCP ALL subtypes or clinical features.
Main Methods:
- Utilized Infinium® MethylationEPIC BeadChip Arrays for high-throughput methylation analysis.
- Analyzed bone marrow samples from pediatric BCP ALL patients (n=38) and healthy controls (n=4).
- Investigated differential methylation patterns across the miRNA geneome.
Main Results:
- Identified significant differential methylation of miRNA genes in pediatric BCP ALL compared to controls.
- Observed a distinct subcluster within BCP ALL patients characterized by the TCF3-PBX1 genetic subtype.
- Found associations between hyper- and hypomethylated miRNA gene sites (promoters and gene bodies) and leukemia-related phenotypes. Top hypermethylated: MIR1273G, MIR1304, MIR663. Top hypomethylated: MIR4442, MIR155, MIR3909.
Conclusions:
- Pediatric BCP ALL exhibits a distinct microRNA gene methylation landscape compared to non-neoplastic controls.
- The TCF3-PBX1 genetic subtype forms a recognizable subcluster within BCP ALL based on methylation profiles.
- Methylation patterns in miRNA genes are linked to leukemia-related phenotypes, highlighting their potential role in BCP ALL pathogenesis.
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