Identification of Recurrent Mutations in the microRNA-Binding Sites of B-Cell Lymphoma-Associated Genes in Follicular Lymphoma.
Int J Mol Sci
; 21(22)2020 Nov 20.
Article
in En
| MEDLINE
| ID: mdl-33233721
ABSTRACT
Follicular lymphoma (FL) is a common indolent B-cell lymphoma that can transform into the more aggressive transformed FL (tFL). However, the molecular process driving this transformation is uncertain. In this work, we aimed to identify microRNA (miRNA)-binding sites recurrently mutated in follicular lymphoma patients, as well as in transformed FL patients. Using whole-genome sequencing data from FL tumors, we discovered 544 mutations located in bioinformatically predicted microRNA-binding sites. We then studied these specific regions using targeted sequencing in a cohort of 55 FL patients, found 16 recurrent mutations, and identified a further 69 variants. After filtering for QC, we identified 21 genes with mutated miRNA-binding sites that were also enriched for B-cell-associated genes by Gene Ontology. Over 40% of mutations identified in these genes were present exclusively in tFL patients. We validated the predicted miRNA-binding sites of five of the genes by luciferase assay and demonstrated that the identified mutations in BCL2 and EZH2 genes impaired the binding efficiency of miR-5008 and miR-144 and regulated the endogenous levels of messenger RNA (mRNA).
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Binding Sites
/
Lymphoma, Follicular
/
Lymphoma, Large B-Cell, Diffuse
/
Proto-Oncogene Proteins c-bcl-2
/
MicroRNAs
/
Enhancer of Zeste Homolog 2 Protein
Type of study:
Diagnostic_studies
/
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Humans
Country/Region as subject:
Europa
Language:
En
Journal:
Int J Mol Sci
Year:
2020
Document type:
Article
Affiliation country:
España