3 research outputs found
Identification of Recurrent Mutations in the microRNA-Binding Sites of B-Cell Lymphoma-Associated Genes in Follicular Lymphoma
: 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)
Identification of Recurrent Mutations in the microRNA-Binding Sites of B-Cell Lymphoma-Associated Genes in Follicular Lymphoma
: 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)