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Identification of novel sequence variations in microRNAs in chronic lymphocytic leukemia
J. Kminkova, M. Mraz, K. Zaprazna, V. Navrkalova, B. Tichy, K. Plevova, J. Malcikova, K. Cerna, T. Rausch, V. Benes, Y. Brychtova, M. Doubek, J. Mayer, S. Pospisilova,
Language English Country England, Great Britain
Document type Journal Article, Research Support, Non-U.S. Gov't
Grant support
NT11218
MZ0
CEP Register
NT13493
MZ0
CEP Register
Digital library NLK
Full text - Article
Full text - Article
Source
Source
NLK
Free Medical Journals
from 1996 to 1 year ago
Open Access Digital Library
from 1996-01-01
Medline Complete (EBSCOhost)
from 1996-01-01 to 1 year ago
PubMed
24306027
DOI
10.1093/carcin/bgt396
Knihovny.cz E-resources
- MeSH
- Alleles MeSH
- Chromosome Aberrations MeSH
- Leukemia, Lymphocytic, Chronic, B-Cell genetics MeSH
- Adult MeSH
- Gene Frequency MeSH
- Genetic Variation * MeSH
- Polymorphism, Single Nucleotide MeSH
- Nucleic Acid Conformation MeSH
- Middle Aged MeSH
- Humans MeSH
- MicroRNAs chemistry genetics MeSH
- Mutation MeSH
- Gene Expression Regulation, Leukemic MeSH
- Sequence Analysis, DNA MeSH
- Aged MeSH
- Immunoglobulin Heavy Chains genetics MeSH
- Germ-Line Mutation MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
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.
References provided by Crossref.org
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