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dc.contributor.authorBenítez-Buelga, Carlos
dc.contributor.authorBaquero, Juan Miguel
dc.contributor.authorVaclova, Tereza
dc.contributor.authorFernández, Victoria
dc.contributor.authorMartín, Paloma
dc.contributor.authorInglada-Perez, Lucia 
dc.contributor.authorUrioste, Miguel 
dc.contributor.authorOsorio, Ana 
dc.contributor.authorBenítez, Javier
dc.identifier.citationOncotarget. 2017;8(70):114626-114636es_ES
dc.description.abstractIn this report, we have tried to gain molecular insight into a single nucleotide polymorphism (SNP) in the NEIL2 gene previously identified as "cancer risk modifier" for BRCA2 mutation carriers. To that end, we studied the role of this SNP (rs804271) on NEIL2 transcriptional regulation, oxidative DNA damage and genome instability in two independent set of samples: The first one was a series of eighty-six BRCA1 and BRCA2 mutation carriers and eighty non-carrier controls in which we evaluated the effect of the SNP on NEIL2 gene expression and oxidative DNA damage accumulation. The second was a set of twenty lymphoblastoid cell lines (LCLs), thirteen BRCA1 mutation carriers and seven non-carriers control, that were used to analyze the correlation between NEIL2 mRNA and/or protein levels, the oxidative and the double stranded break (DSB) DNA damage levels. Our results suggest that an excessive production of NEIL2 enzyme, associated with the SNP, may have a deleterious effect modifying cancer risk susceptibility in BRCA2 mutation carriers. We hypothesize that due to the SNP impact on NEIL2 transcriptional upregulation, a cascade of events may converge in the accumulation of oxidative DNA damage and its posterior conversion into DSBs for this specific group of patients.es_ES
dc.description.sponsorshipWe thank Alicia Barroso her technical assistance. Also to Dr. Thomas Helleday, (Karolinska Institutet, Stockholm, Sweden) that kindly provided NEIL2 and UNG purified enzymes. The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health. Additional funds were provided by the NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. Donors were enrolled at Biospecimen Source Sites funded by NCI/SAIC-Frederick, Inc. (SAIC-F) subcontracts to the National Disease Research Interchange (10XS170),Roswell Park Cancer Institute (10XS171), and Science Care, Inc. (X10S172). The Laboratory, Data Analysis, and Coordinating Center (LDACC) were funded through a contract (HHSN268201000029C) to The Broad Institute, Inc. Biorepository operations were funded through an SAIC-F subcontract to the Van Andel Institute (10ST1035). Additional data repository and project management were provided by SAIC-F (HHSN261200800001E). The Brain Bank was supported by supplements to University of Miami grants DA006227 & DA033684 and to contract N01MH000028. Statistical Methods development grants were made to the University of Geneva (MH090941 & MH101814), the University of Chicago (MH090951, MH090937, MH101820, MH101825), the University of North Carolina - Chapel Hill (MH090936 & MH101819), Harvard University (MH090948), Stanford University (MH101782), Washington University St Louis (MH101810), and the University of Pennsylvania (MH101822). The data used for the analyses described in this manuscript were obtained from: [insert, where appropriate] the GTEx Portal on 01/12/2015 and/or dbGaP accession number phs000424.v7.p2 on 01/10/2017.es_ES
dc.publisherImpact Journalses_ES
dc.relation.isversionofPublisher's versiones_ES
dc.subjectBRCA1 and BRCA2es_ES
dc.subjectNEIL2 polymorphism cancer risk modifieres_ES
dc.subjectmRNA levelses_ES
dc.subjectoxidative DNA damagees_ES
dc.subject.meshGenes, BRCA1 es_ES
dc.subject.meshGenes, BRCA2 es_ES
dc.subject.meshPolymorphism, Genetices_ES
dc.titleGenetic variation in the NEIL2 DNA glycosylase gene is associated with oxidative DNA damage in BRCA2 mutation carrierses_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.contributor.funderMinisterio de Economía y Competitividad (España)es_ES
dc.contributor.funderEuropean Regional Development Fund (ERDF/FEDER)es_ES
dc.contributor.funderFondo de Investigaciones Sanitariases_ES
dc.contributor.funderCentro de Investigación Biomedica en Red - CIBERes_ES
dc.repisalud.orgCNIOCNIO::Grupos de investigación::Grupo de Genética Humanaes_ES

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