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RNA-Seq reveals the existence of a CDKN1C-E2F1-TP53 axis that is altered in human T-cell lymphoblastic lymphomas
Author
López Nieva, María Pilar; Fernández-Navarro, Pablo; Vaquero Lorenzo, Concepción; Villa Morales, María del Consuelo; Graña-Castro, Osvaldo; Cobos Fernández, María Ángeles; López-Lorenzo, José Luis; Llamas Sillero, Pilar; González-Sánchez, Laura; Sastre, Isabel; Pollán Santamaría, Marina Anunciación; Malumbres, Marcos; Santos, Javier; Fernández Piqueras, JoséEntity
UAM. Departamento de Biología; UAM. Departamento de Medicina Preventiva y Salud Pública y Microbiología; Centro de Biología Molecular Severo Ochoa (CBM); Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD)Publisher
BioMed CentralDate
2018-04-16Citation
10.1186/s12885-018-4304-y
BMC Cancer 18.1 (2018): 430
ISSN
1471-2407DOI
10.1186/s12885-018-4304-yFunded by
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 acknowledgedProject
Gobierno de España. SAF2015–70561-R; Comunidad de Madrid. B2017/BMD-3778/LINFOMASEditor's Version
https://doi.org/10.1186/s12885-018-4304-ySubjects
CDKN1C-E2F1-TP53 deregulation; Deregulation of miRNAs; Promoter hypermethylation; T-cell lymphoblastic lymphoma; Biología y Biomedicina / BiologíaRights
© 2018 The Author(s)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
Files in this item
Google Scholar:López Nieva, María Pilar
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Fernández-Navarro, Pablo
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Vaquero Lorenzo, Concepción
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Villa Morales, María del Consuelo
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Graña-Castro, Osvaldo
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Cobos Fernández, María Ángeles
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López-Lorenzo, José Luis
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Llamas Sillero, Pilar
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González-Sánchez, Laura
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Sastre, Isabel
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Pollán Santamaría, Marina Anunciación
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Malumbres, Marcos
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Santos, Javier
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Fernández Piqueras, José
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