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dc.contributor.authorNovillo, Apolonia
dc.contributor.authorFernández-Santander, Ana
dc.contributor.authorGaibar, Maria
dc.contributor.authorGalán, Miguel
dc.contributor.authorRomero-Lorca, Alicia
dc.contributor.authorEl Abdellaoui-Soussi, Fadoua
dc.contributor.authorGómez-del Arco, Pablo
dc.date.accessioned2021-05-24T16:41:54Z
dc.date.available2021-05-24T16:41:54Z
dc.date.issued2021-04-26
dc.identifier.citationFront Oncol. 2021 Apr 26;11:633233.es_ES
dc.identifier.issn2234-943Xes_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/13008
dc.description.abstractChromodomain-helicase-DNA-binding protein 4 (CHD4) is an epigenetic regulator identified as an oncogenic element that may provide a novel therapeutic target for the treatment of breast cancer (BC). CHD4-the core component of the nucleosome remodeling and deacetylase (NuRD) complex-may be mutated in patients with this disease. However, information on CHD4 mutants that might allow their use as biomarkers of therapeutic success and prognosis is lacking. The present work examines mutations in CHD4 reported in patients with breast cancer and included in public databases and attempts to identify their roles in its development. The databases revealed 81 point mutations across different types of breast cancer (19 of which also appeared in endometrial, intestinal, nervous system, kidney, and lymphoid organ cancers). 71.6% of the detected mutations were missense mutations, 13.6% were silent, and 6.2% nonsense. Over 50% affected conserved residues of the ATPase motor (ATPase and helicase domains), and domains of unknown function in the C-terminal region. Thirty one mutations were classified in the databases as either 'deleterious', 'probably/possibly damaging' or as 'high/medium pathogenic'; another five nonsense and one splice-site variant were predicted to produce potentially harmful truncated proteins. Eight of the 81 mutations were categorized as putative driver mutations and have been found in other cancer types. Some mutations seem to influence ATPase and DNA translocation activities (R1162W), while others may alter protein stability (R877Q/H, R975H) or disrupt DNA binding and protein activity (R572*, X34_splice) suggesting CHD4 function may be affected. In vivo tumorigenecity studies in endometrial cancer have revealed R975H and R1162W as mutations that lead to CHD4 loss-of-function. Our study provides insight into the molecular mechanism whereby CHD4, and some of its mutants could play a role in breast cancer and suggest important implications for the biological comprehension and prognosis of breast cancer, identifying CHD4 as a novel therapeutic target for BC patients.es_ES
dc.description.sponsorshipPG-A is supported by Ministry of Science and Innovation of Spain MICINN (grant no. SAF2016-77816-P). AN, AF-S, MaG, and AR-L are supported by the Fundación de la Universidad Europea (project numbers XSAN001907 and XFGU001903). FA-S is a recipient of a fellowship from the MICINN (no. BES-2017-080629).es_ES
dc.language.isoenges_ES
dc.publisherFrontiers Media es_ES
dc.relation.isversionofPublisher's versiones_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectCHD4 genees_ES
dc.subjectBreast canceres_ES
dc.subjectChromatin remodelinges_ES
dc.subjectMutationes_ES
dc.subjectTherapies in breast canceres_ES
dc.titleRole of Chromodomain-Helicase-DNA-Binding Protein 4 (CHD4) in Breast Canceres_ES
dc.typeArtículoes_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID33981601es_ES
dc.format.volume11es_ES
dc.format.page633233es_ES
dc.identifier.doi10.3389/fonc.2021.633233es_ES
dc.contributor.funderMinisterio de Ciencia e Innovación (España)
dc.contributor.funderFundación de la Universidad Europea
dc.description.peerreviewedes_ES
dc.identifier.e-issn2234-943Xes_ES
dc.relation.publisherversionhttps://doi.org/10.3389/fonc.2021.633233es_ES
dc.identifier.journalFrontiers In Oncologyes_ES
dc.repisalud.centroISCIII::Instituto de Investigación de Enfermedades Rarases_ES
dc.repisalud.institucionISCIIIes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2016-77816-Pes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/BES-2017-080629es_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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