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dc.contributor.authorLarrea, Erika
dc.contributor.authorFernandez-Mercado, Marta
dc.contributor.authorGuerra-Assunção, José Afonso
dc.contributor.authorWang, Jun
dc.contributor.authorGoicoechea, Ibai
dc.contributor.authorGaafar, Ayman
dc.contributor.authorCeberio, Izaskun
dc.contributor.authorLobo, Carmen
dc.contributor.authorOkosun, Jessica
dc.contributor.authorEnright, Anton J.
dc.contributor.authorFitzgibbon, Jude
dc.contributor.authorLawrie, Charles H.
dc.date.accessioned2020-11-23T04:10:34Z
dc.date.available2020-11-23T04:10:34Z
dc.date.issued2020-11-20
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/313214
dc.description.abstractFollicular 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).
dc.languageen
dc.publisherMDPI
dc.subjectfollicular lymphoma (FL)
dc.subjectdiffuse large B-cell lymphoma (DLBCL)
dc.subjectmicroRNA
dc.subjectmutation
dc.titleIdentification of Recurrent Mutations in the microRNA-Binding Sites of B-Cell Lymphoma-Associated Genes in Follicular Lymphoma
dc.typeArticle
dc.date.updated2020-11-23T04:10:34Z
prism.issueIdentifier22
prism.publicationNameInternational Journal of Molecular Sciences
prism.volume21
dc.identifier.doi10.17863/CAM.60320
dcterms.dateAccepted2020-11-18
rioxxterms.versionofrecord10.3390/ijms21228795
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidFernandez-Mercado, Marta [0000-0003-3458-9231]
dc.contributor.orcidGuerra-Assunção, José Afonso [0000-0001-6593-403X]
dc.contributor.orcidWang, Jun [0000-0003-2509-9599]
dc.contributor.orcidOkosun, Jessica [0000-0001-6021-5044]
dc.contributor.orcidLawrie, Charles H. [0000-0002-8882-1131]
dc.identifier.eissn1422-0067


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