Identification of novel sequence variations in microRNAs in chronic lymphocytic leukemia
| Authors | |
|---|---|
| Year of publication | 2014 |
| Type | Article in Periodical |
| Magazine / Source | Carcinogenesis |
| MU Faculty or unit | |
| Citation | |
| Web | http://carcin.oxfordjournals.org/content/early/2013/12/03/carcin.bgt396.full.pdf+html |
| Doi | http://dx.doi.org/10.1093/carcin/bgt396 |
| Field | Oncology and hematology |
| Keywords | PAPILLARY THYROID-CARCINOMA; COLORECTAL-CANCER; HEPATOCELLULAR-CARCINOMA; FUNCTIONAL POLYMORPHISM; DROSHA-DGCR8 COMPLEX; EXPRESSION; RNA; RISK; GENES; SURVIVAL |
| Attached files | |
| Description | We have analyzed the miRNA sequence variations in patients with CLL and the effect of these variations on their secondary structure and expression.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. |
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