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oai:repisalud.isciii.es:20.500.12105/66562025-05-20T08:36:57Zcom_20.500.12105_2052com_20.500.12105_2051com_20.500.12105_2173com_20.500.12105_15322col_20.500.12105_19608col_20.500.12105_19597col_20.500.12105_16977

00925njm 22002777a 4500 dc López-Nieva, Pilar author Fernandez-Navarro, Pablo L author Vaquero-Lorenzo, Concepción author Villa-Morales, María author Graña Castro, Osvaldo author Cobos-Fernández, María Ángeles author López-Lorenzo, José Luis author Llamas, Pilar author González-Sanchez, Laura author Sastre, Isabel author Pollan-Santamaria, Marina author Malumbres Martinez, Marcos author Santos, Javier author Fernández-Piqueras, José author 2018-04-16 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. BMC Cancer. 2018 Apr 16;18(1):430. 1471-2407 http://hdl.handle.net/20.500.12105/6656 29661169 10.1186/s12885-018-4304-y 1471-2407 BMC cancer CDKN1C-E2F1-TP53 deregulation Deregulation of miRNAs Promoter hypermethylation T-cell lymphoblastic lymphoma RNA-Seq reveals the existence of a CDKN1C-E2F1-TP53 axis that is altered in human T-cell lymphoblastic lymphomas