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dc.contributor.author | Delgado, Pilar | |
dc.contributor.author | Alvarez-Prado, Angel Francisco | |
dc.contributor.author | Marina-Zarate, Ester | |
dc.contributor.author | Sernandez, Isora V. | |
dc.contributor.author | Mur, Sonia M. | |
dc.contributor.author | de la Barrera, Jorge | |
dc.contributor.author | Sanchez-Cabo, Fatima | |
dc.contributor.author | Cañamero, Marta | |
dc.contributor.author | Molina-Iracheta, Antonio | |
dc.contributor.author | Belver, Laura | |
dc.contributor.author | de Yebenes, Virginia G | |
dc.contributor.author | Ramiro, Almudena R | |
dc.date.accessioned | 2021-07-19T12:00:16Z | |
dc.date.available | 2021-07-19T12:00:16Z | |
dc.date.issued | 2020-12 | |
dc.identifier.citation | PLoS Genet. 2020; 16(12):e1008960 | es_ES |
dc.identifier.issn | 1553-7404 | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/13248 | |
dc.description.abstract | Most B cell lymphomas originate from B cells that have germinal center (GC) experience and bear chromosome translocations and numerous point mutations. GC B cells remodel their immunoglobulin (Ig) genes by somatic hypermutation (SHM) and class switch recombination (CSR) in their Ig genes. Activation Induced Deaminase (AID) initiates CSR and SHM by generating U:G mismatches on Ig DNA that can then be processed by Uracyl-N-glycosylase (UNG). AID promotes collateral damage in the form of chromosome translocations and off-target SHM, however, the exact contribution of AID activity to lymphoma generation and progression is not completely understood. Here we show using a conditional knock-in strategy that AID supra-activity alone is not sufficient to generate B cell transformation. In contrast, in the absence of UNG, AID supra-expression increases SHM and promotes lymphoma. Whole exome sequencing revealed that AID heavily contributes to lymphoma SHM, promoting subclonal variability and a wider range of oncogenic variants. Thus, our data provide direct evidence that UNG is a brake to AID-induced intratumoral heterogeneity and evolution of B cell lymphoma. | es_ES |
dc.description.sponsorship | PD was supported by the AECC foundation (AIO2012). EM-Z is an FPI fellow (BES-2014-069525). AFA-P, S.M.M. and A.R.R. are supported by CNIC funding. This project was funded by the Spanish Ministerio de Economıa, Industria y Competitividad SAF2013-42767-R, SAF2016-75511-R, and European Research Council StG BCLYM, to A.R.R. The CNIC is supported by the Ministerio de Ciencia, Innovacion y Universidades and the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Public Library of Science (PLOS) | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject.mesh | Genetic Heterogeneity | es_ES |
dc.subject.mesh | Animals | es_ES |
dc.subject.mesh | Cell Transformation, Neoplastic | es_ES |
dc.subject.mesh | Cells, Cultured | es_ES |
dc.subject.mesh | Clonal Evolution | es_ES |
dc.subject.mesh | Cytidine Deaminase | es_ES |
dc.subject.mesh | Female | es_ES |
dc.subject.mesh | Lymphoma, B-Cell | es_ES |
dc.subject.mesh | Male | es_ES |
dc.subject.mesh | Mice | es_ES |
dc.subject.mesh | Mice, Inbred C57BL | es_ES |
dc.subject.mesh | Mutation | es_ES |
dc.subject.mesh | Uracil-DNA Glycosidase | es_ES |
dc.title | Interplay between UNG and AID governs intratumoral heterogeneity in mature B cell lymphoma. | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 33362210 | es_ES |
dc.format.volume | 16 | es_ES |
dc.format.number | 12 | es_ES |
dc.format.page | e1008960 | es_ES |
dc.identifier.doi | 10.1371/journal.pgen.1008960 | es_ES |
dc.description.peerreviewed | Sí | es_ES |
dc.relation.publisherversion | https://doi.org/10.1371/journal.pgen.1008960 | es_ES |
dc.identifier.journal | PLoS genetics | es_ES |
dc.repisalud.orgCNIC | CNIC::Unidades técnicas::Bioinformática | es_ES |
dc.repisalud.orgCNIC | CNIC::Unidades técnicas::Medicina Comparativa | es_ES |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Biología de linfocitos B | es_ES |
dc.repisalud.institucion | CNIC | es_ES |
dc.rights.accessRights | open access | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/AIO2012 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/BES-2014-069525 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/SAF2013-42767-R | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/SAF2016-75511-R | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/SEV-2015-0505 | es_ES |