Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/163952
Share/Export:
logo share SHARE logo core CORE BASE
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE
Title

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

AuthorsLópez-Nieva, Pilar CSIC ORCID; Fernández-Navarro, Pablo; Vaquero-Lorenzo, Concepción; Villa-Morales, María CSIC ORCID; Graña-Castro, Osvaldo; Cobos-Fernández, M. A. CSIC; López-Lorenzo, José L.; Llamas, Pilar; González-Sánchez, Laura CSIC ORCID; Sastre, Isabel CSIC ORCID; Pollan, Marina; Malumbres, Marcos; Santos, Javier CSIC ORCID; Fernández-Piqueras, José CSIC ORCID
Issue Date16-Apr-2018
PublisherBioMed Central
CitationBMC Cancer 18(1): 430 (2018)
AbstractAbstract 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.
Publisher version (URL)https://doi.org/10.1186/s12885-018-4304-y
URIhttp://hdl.handle.net/10261/163952
DOI10.1186/s12885-018-4304-y
Appears in Collections:(CBM) Artículos

Files in This Item:
File Description SizeFormat
12885_2018_Article_4304.pdf2,42 MBAdobe PDFThumbnail
View/Open
Show full item record
Review this work

WEB OF SCIENCETM
Citations

5
checked on Dec 2, 2021

Google ScholarTM

Check

Altmetric

Dimensions


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.