title: Identification of novel sequence variations in microRNAs in chronic lymphocytic leukemia.
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.
authors.affiliation: CEITEC - Central European Institute of Technology, Center of Molecular Medicine, Masaryk University, Brno 625 00, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Kminkova
authors.forename: Marek
authors.initials: M
authors.lastname: Mraz
authors.forename: Kristina
authors.initials: K
authors.lastname: Zaprazna
authors.forename: Veronika
authors.initials: V
authors.lastname: Navrkalova
authors.forename: Boris
authors.initials: B
authors.lastname: Tichy
authors.forename: Karla
authors.initials: K
authors.lastname: Plevova
authors.forename: Jitka
authors.initials: J
authors.lastname: Malcikova
authors.forename: Katerina
authors.initials: K
authors.lastname: Cerna
authors.forename: Tobias
authors.initials: T
authors.lastname: Rausch
authors.forename: Vladimir
authors.initials: V
authors.lastname: Benes
authors.forename: Yvona
authors.initials: Y
authors.lastname: Brychtova
authors.forename: Michael
authors.initials: M
authors.lastname: Doubek
authors.forename: Jiri
authors.initials: J
authors.lastname: Mayer
authors.forename: Sarka
authors.initials: S
authors.lastname: Pospisilova
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D002869:Chromosome Aberrations; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D005787:Gene Frequency; D014644:Genetic Variation; D018095:Germ-Line Mutation; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009690:Nucleic Acid Conformation; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA
chemical_list: D007143:Immunoglobulin Heavy Chains; C505362:MIRN16 microRNA, human; C532045:MIRN29a microRNA, human; D035683:MicroRNAs