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Updated: May 5, 2026
Comprehensive DNA Methylation Analysis Using a Methyl-CpG-binding Domain Capture-based Method in Chronic Lymphocytic Leukemia Patients
Published on: June 16, 2017
Identification of novel sequence variations in microRNAs in chronic lymphocytic leukemia
Jana Kminkova1, Marek Mraz, Kristina Zaprazna
1CEITEC - Central European Institute of Technology, Center of Molecular Medicine, Masaryk University, Brno 625 00, Czech Republic.
Abstract:
MicroRNA (miRNA) expression is deregulated in many tumors including chronic lymphocytic leukemia (CLL). Although the particular mechanism(s) responsible for their aberrant expression is not well characterized, the presence of mutations and single-nucleotide polymorphisms (SNPs) in miRNA genes, possibly affecting their secondary structure and expression, has been described. In CLL; however, the impact and frequency of such variations have yet to be elucidated. Using a custom resequencing microarray, we screened sequence variations in 109 cancer-related pre-miRNAs in 98 CLL patients. Additionally, the primary regions of miR-29b-2/29c and miR-16-1 were analyzed by Sanger sequencing in another cohort of 213 and 193 CLL patients, respectively. Altogether, we describe six novel miR-sequence variations and the presence of SNPs (n = 27), most of which changed the miR-secondary structure. Moreover, some of the identified SNPs have a significantly different frequency in CLL when compared with a control population. Additionally, we identified a novel variation in miR-16-1 that had not been described previously in CLL patients. We show that this variation affects the expression of mature miR-16-1. We also show that the expression of another miRNA with pathogenetic relevance for CLL, namely miR-29b-2, is influenced by the presence of a polymorphic insertion, which is more frequent in CLL than in a control population. Altogether, these data suggest that sequence variations may occur during CLL development and/or progression.
Insights
Sequence variations in microRNA (miRNA) genes are linked to chronic lymphocytic leukemia (CLL). Researchers found novel variations and single-nucleotide polymorphisms (SNPs) affecting miRNA structure and expression in CLL patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNA (miRNA) expression is frequently deregulated in tumors, including chronic lymphocytic leukemia (CLL).
- Mechanisms driving aberrant miRNA expression in CLL are not fully understood, but mutations and single-nucleotide polymorphisms (SNPs) in miRNA genes are potential contributors.
- The impact and prevalence of sequence variations in miRNA genes within CLL remain largely uncharacterized.
Purpose of the Study:
- To investigate the frequency and impact of sequence variations, including SNPs, in cancer-related microRNA genes in patients with chronic lymphocytic leukemia (CLL).
- To identify novel miRNA sequence variations and assess their effect on miRNA secondary structure and expression levels in CLL.
- To compare the frequency of identified variations in CLL patients versus a control population.
Main Methods:
- Screening of sequence variations in 109 cancer-related pre-miRNAs using a custom resequencing microarray in 98 CLL patients.
- Sanger sequencing of primary regions of miR-29b-2/29c and miR-16-1 in independent cohorts of CLL patients (n=213 and n=193, respectively).
- Analysis of identified variations for their impact on miRNA secondary structure and expression, and comparison of SNP frequencies with control populations.
Main Results:
- Identification of six novel miR-sequence variations and 27 SNPs, with most altering the miRNA secondary structure.
- Significant differences in the frequency of certain identified SNPs between CLL patients and a control population.
- Discovery of a novel variation in miR-16-1 affecting mature miR-16-1 expression and identification of a polymorphic insertion in miR-29b-2, more frequent in CLL, influencing its expression.
Conclusions:
- Sequence variations in microRNA genes are present in chronic lymphocytic leukemia (CLL) and can affect miRNA structure and expression.
- These variations, including novel findings in miR-16-1 and miR-29b-2, may play a role in the development and/or progression of CLL.
- The study highlights the potential significance of miRNA sequence variations as a contributing factor in CLL pathogenesis.
