RNA-Seq reveals the existence of a CDKN1C-E2F1-TP53 axis that is altered in human T-cell lymphoblastic lymphomas

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dc.contributor.author López-Nieva, Pilar
dc.contributor.author Fernández-Navarro, Pablo
dc.contributor.author Vaquero-Lorenzo, Concepción
dc.contributor.author Villa-Morales, María
dc.contributor.author Graña-Castro, Osvaldo
dc.contributor.author Cobos Fernández, María Ángeles
dc.contributor.author López-Lorenzo, José Luis
dc.contributor.author Llamas, Pilar
dc.contributor.author González-Sánchez, Laura
dc.contributor.author Sastre, Isabel
dc.contributor.author Pollan, Marina
dc.contributor.author Malumbres, Marcos
dc.contributor.author Santos, Javier
dc.contributor.author Fernández-Piqueras, José
dc.contributor.other UAM. Departamento de Biología es_ES
dc.contributor.other UAM. Departamento de Medicina Preventiva y Salud Pública y Microbiología es_ES
dc.contributor.other Centro de Biología Molecular Severo Ochoa (CBMSO) es_ES
dc.contributor.other Instituto de Investigación Sanitaria Fundación Jiménez Díaz (ISS-FJD) es_ES
dc.date.accessioned 2018-06-26T16:28:01Z
dc.date.available 2018-06-26T16:28:01Z
dc.date.issued 2018-04-16
dc.identifier.citation BMC Cancer 18.1 (2018): 430 es_ES
dc.identifier.issn 1471-2407 es_ES
dc.identifier.uri http://hdl.handle.net/10486/683392
dc.description.abstract Background: Precursor T-cell lymphoblastic lymphomas (T-LBL) are rare aggressive hematological malignancies that mainly develop in children. As in other cancers, the loss of cell cycle control plays a prominent role in the pathogenesis in these malignancies that is primarily attributed to loss of CDKN2A (encoding protein p16INK4A). However, the impact of the deregulation of other genes such as CDKN1C, E2F1, and TP53 remains to be clarified. Interestingly, experiments in mouse models have proven that conditional T-cell specific deletion of Cdkn1c gene may induce a differentiation block at the DN3 to DN4 transition, and that the loss of this gene in the absence of Tp53 led to aggressive thymic lymphomas. Results: In this manuscript, we demonstrated that the simultaneous deregulation of CDKN1C, E2F1, and TP53 genes by epigenetic mechanisms and/or the deregulation of specific microRNAs, together with additional impairing of TP53 function by the expression of dominant-negative isoforms are common features in primary human T-LBLs. Conclusions: Previous experimental work in mice revealed that T-cell specific deletion of Cdkn1c accelerates lymphomagenesis in the absence of Tp53. If, as expected, the consequences of the deregulation of the CDKN1C-E2F1-TP53 axis were the same as those experimentally demonstrated in mouse models, the disruption of this axis might be useful to predict tumor aggressiveness, and to provide the basis towards the development of potential therapeutic strategiesin human T-LBL es_ES
dc.description.sponsorship The authors would like to thank the Spanish Ministry of Economy and Competitiveness (SAF2015–70561-R; MINECO/FEDER, EU) and the Autonomous Community of Madrid, Spain (B2017/BMD-3778; LINFOMAS-CM) for funding this work. Institutional grants from the Fundación Ramón Areces and Banco de Santander are also acknowledged en_US
dc.format.extent 12 pag. es_ES
dc.format.mimetype application/pdf en
dc.language.iso eng en
dc.publisher BioMed Central en_US
dc.relation.ispartof BMC Cancer en_US
dc.rights © 2018 The Author(s) en_US
dc.subject.other CDKN1C-E2F1-TP53 deregulation en_US
dc.subject.other Deregulation of miRNAs en_US
dc.subject.other Promoter hypermethylation en_US
dc.subject.other T-cell lymphoblastic lymphoma en_US
dc.title RNA-Seq reveals the existence of a CDKN1C-E2F1-TP53 axis that is altered in human T-cell lymphoblastic lymphomas en_US
dc.type article en
dc.subject.eciencia Biología y Biomedicina / Biología es_ES
dc.relation.publisherversion https://doi.org/10.1186/s12885-018-4304-y es_ES
dc.identifier.doi 10.1186/s12885-018-4304-y es_ES
dc.identifier.publicationfirstpage 430-1 es_ES
dc.identifier.publicationissue 1 es_ES
dc.identifier.publicationlastpage 430-12 es_ES
dc.identifier.publicationvolume 18 es_ES
dc.relation.projectID Gobierno de España. SAF2015–70561-R es_ES
dc.relation.projectID Comunidad de Madrid. B2017/BMD-3778/LINFOMAS es_ES
dc.type.version info:eu-repo/semantics/publishedVersion en
dc.rights.cc Reconocimiento es_ES
dc.rights.accessRights openAccess en
dc.authorUAM Cobos Fernández, María Ángeles (264568)
dc.authorUAM Llamas Sillero, Pilar (261170)
dc.authorUAM Pollán Santamaría, Marina Anunciación (262007)

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