Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/6810
RNA-Seq reveals the existence of a CDKN1C-E2F1-TP53 axis that is altered in human T-cell lymphoblastic lymphomas
López-Nieva, Pilar | Fernandez-Navarro, Pablo ISCIII | Vaquero-Lorenzo, Concepción | Villa-Morales, María | Graña-Castro, Osvaldo CNIO | Cobos-Fernández, María Ángeles | López-Lorenzo, José Luis | Llamas, Pilar | González-Sanchez, Laura | Sastre, Isabel | Pollan-Santamaria, Marina ISCIII | Malumbres Martinez, Marcos CNIO | Santos, Javier | Fernández-Piqueras, José
BMC Cancer. 2018 Apr 16;18(1):430
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.
CDKN1C-E2F1-TP53 deregulation | Deregulation of miRNAs | Promoter hypermethylation | T-cell lymphoblastic lymphoma
Adolescent | Adult | Animals | Child | Cyclin-Dependent Kinase Inhibitor p57 | E2F1 Transcription Factor | Epigenesis, Genetic | Female | Gene Expression Regulation, Neoplastic | Humans | Male | Mice | Precursor T-Cell Lymphoblastic Leukemia-Lymphoma | Sequence Analysis, RNA | Signal Transduction | Tumor Suppressor Protein p53 | Young Adult
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