دورية أكاديمية
RNA-Seq reveals the existence of a CDKN1C-E2F1-TP53 axis that is altered in human T-cell lymphoblastic lymphomas
| العنوان: | RNA-Seq reveals the existence of a CDKN1C-E2F1-TP53 axis that is altered in human T-cell lymphoblastic lymphomas |
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| المؤلفون: | López-Nieva, Pilar, Fernandez-Navarro, Pablo L, Vaquero-Lorenzo, Concepción, Villa-Morales, María, Graña Castro, Osvaldo, Cobos-Fernández, María Ángeles, López-Lorenzo, José Luis, Llamas, Pilar, González-Sanchez, Laura, Sastre, Isabel, Pollan-Santamaria, Marina, Malumbres Martinez, Marcos, Santos, Javier, Fernández-Piqueras, José |
| المساهمون: | Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), Comunidad de Madrid (España), Fundación Ramón Areces, Banco Santander, Ministerio de Economía y Competitividad (España) |
| بيانات النشر: | BioMed Central (BMC) |
| سنة النشر: | 2018 |
| المجموعة: | REPISALUD (REPositorio Institucional en SALUD del Instituto de Salud Carlos III - ISCIII) |
| مصطلحات موضوعية: | 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 |
| الوصف: | 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. ; The authors would like to thank Mario González-Sánchez and Javier González-Palacios ("Bioinformatics and Research Group in Genetic and Environmental Epidemiology", ISCIII) for their technical support. We thank all patients who were willing to donate their sample without their support the research work would not be possible ; Sí |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1471-2407 |
| العلاقة: | https://doi.org/10.1186/s12885-018-4304-yTest.; info:eu-repo/grantAgreement/ES/SAF2015-70561-R; BMC Cancer. 2018 Apr 16;18(1):430.; http://hdl.handle.net/20.500.12105/6656Test; BMC cancer |
| DOI: | 10.1186/s12885-018-4304-y |
| الإتاحة: | https://doi.org/20.500.12105/6656Test https://doi.org/10.1186/s12885-018-4304-yTest https://hdl.handle.net/20.500.12105/6656Test |
| حقوق: | http://creativecommons.org/licenses/by/4.0Test/ ; Atribución 4.0 Internacional ; open access |
| رقم الانضمام: | edsbas.25BC9FAA |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 14712407 |
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| DOI: | 10.1186/s12885-018-4304-y |