Publicació científica

S'han trobat 1424 publicacions amb els criteris indicats.
Genescà E, Morgades M, Montesinos P, Barba P, Gil C, Guàrdia R, Moreno MJ, Martínez-Carballeira D, García-Cadenas I, Vives S, Ribera J, González-Campos J, González-Gil C, Zamora L, Ramírez JL, Díaz-Beya M, Mercadal S, Artola MT, Cladera A, Tormo M, Bermúdez A, Vall-Llovera F, Martínez P, Amigo ML, Monsalvo S, Novo A, Cervera M, García-Guiñon A, Juncà J, Ciudad J, Orfao A, Ribera JM

Unique clinico-biological, genetic and prognostic features of adult early T cell precursor acute lymphoblastic leukemia.

Haematologica 19 Set 2019, . Epub 19 Set 2019Més informació
Bueno C, Tejedor JR, Bashford-Rogers R, González-Silva L, Valdés-Mas R, Agraz-Doblás A, Díaz de la Guardia R, Ribera J, Zamora L, Bilhou-Nabera C, Abermil N, Guermouche H, Gouache E, Leverger G, Fraga MF, Fernández AF, Ballerini P, Varela I, Menendez P

Natural history and cell of origin of TC F3-ZN F384 and PTPN11 mutations in monozygotic twins with concordant BCP-ALL

Blood 12 Set 2019, 134 (11) 900-905. Epub 20 Jun 2019Més informació
Oliveira-Mateos C, Sánchez-Castillo A, Soler M, Obiols-Guardia A, Piñeyro D, Boque-Sastre R, Calleja-Cervantes ME, Castro de Moura M, Martínez-Cardús A, Rubio T, Pelletier J, Martínez-Iniesta M, Herrero-Martín D, Tirado OM, Gentilella A, Villanueva A, Esteller M, Farré L, Guil S

The transcribed pseudogene RPSAP52 enhances the oncofetal HMGA2-IGF2BP2-RAS axis through LIN28B-dependent and independent let-7 inhibition.

Nat Commun 4 Set 2019, 10 (1) 3979. Epub 4 Set 2019
One largely unknown question in cell biology is the discrimination between inconsequential and functional transcriptional events with relevant regulatory functions. Here, we find that the oncofetal HMGA2 gene is aberrantly reexpressed in many tumor types together with its antisense transcribed pseudogene RPSAP52. RPSAP52 is abundantly present in the cytoplasm, where it interacts with the RNA binding protein IGF2BP2/IMP2, facilitating its binding to mRNA targets, promoting their translation by mediating their recruitment on polysomes and enhancing proliferative and self-renewal pathways. Notably, downregulation of RPSAP52 impairs the balance between the oncogene LIN28B and the tumor suppressor let-7 family of miRNAs, inhibits cellular proliferation and migration in vitro and slows down tumor growth in vivo. In addition, high levels of RPSAP52 in patient samples associate with a worse prognosis in sarcomas. Overall, we reveal the roles of a transcribed pseudogene that may display properties of an oncofetal master regulator in human cancers.
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Cornet-Masana JM, Banús-Mulet A, Carbó JM, Torrente MÁ, Guijarro F, Cuesta-Casanovas L, Esteve J, Risueño RM

Dual lysosomal-mitochondrial targeting by antihistamines to eradicate leukaemic cells.

EBioMedicine Set 2019, 47 221-234. Epub 28 Ago 2019
Despite great efforts to identify druggable molecular targets for AML, there remains an unmet need for more effective therapies.
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Dong X, Zhang R, He J, Lai L, Alolga RN, Shen S, Zhu Y, You D, Lin L, Chen C, Zhao Y, Duan W, Su L, Shafer A, Salama M, Fleischer T, Bjaanæs MM, Karlsson A, Planck M, Wang R, Staaf J, Helland Å, Esteller M, Wei Y, Chen F, Christiani DC

Trans-omics biomarker model improves prognostic prediction accuracy for early-stage lung adenocarcinoma.

Aging (Albany NY) 21 Ago 2019, 11 (16) 6312-6335. Epub 21 Ago 2019
Limited studies have focused on developing prognostic models with trans-omics biomarkers for early-stage lung adenocarcinoma (LUAD). We performed integrative analysis of clinical information, DNA methylation, and gene expression data using 825 early-stage LUAD patients from 5 cohorts. Ranger algorithm was used to screen prognosis-associated biomarkers, which were confirmed with a validation phase. Clinical and biomarker information was fused using an iCluster plus algorithm, which significantly distinguished patients into high- and low-mortality risk groups (
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Janin M, Ortiz-Barahona V, de Moura MC, Martínez-Cardús A, Llinàs-Arias P, Soler M, Nachmani D, Pelletier J, Schumann U, Calleja-Cervantes ME, Moran S, Guil S, Bueno-Costa A, Piñeyro D, Perez-Salvia M, Rosselló-Tortella M, Piqué L, Bech-Serra JJ, De La Torre C, Vidal A, Martínez-Iniesta M, Martín-Tejera JF, Villanueva A, Arias A, Cuartas I, Aransay AM, La Madrid AM, Carcaboso AM, Santa-Maria V, Mora J, Fernandez AF, Fraga MF, Aldecoa I, Pedrosa L, Graus F, Vidal N, Martínez-Soler F, Tortosa A, Carrato C, Balañá C, Boudreau MW, Hergenrother PJ, Kötter P, Entian KD, Hench J, Frank S, Mansouri S, Zadeh G, Dans PD, Orozco M, Thomas G, Blanco S, Seoane J, Preiss T, Pandolfi PP, Esteller M

Epigenetic loss of RNA-methyltransferase NSUN5 in glioma targets ribosomes to drive a stress adaptive translational program.

Acta Neuropathol. 19 Ago 2019, . Epub 19 Ago 2019
Tumors have aberrant proteomes that often do not match their corresponding transcriptome profiles. One possible cause of this discrepancy is the existence of aberrant RNA modification landscapes in the so-called epitranscriptome. Here, we report that human glioma cells undergo DNA methylation-associated epigenetic silencing of NSUN5, a candidate RNA methyltransferase for 5-methylcytosine. In this setting, NSUN5 exhibits tumor-suppressor characteristics in vivo glioma models. We also found that NSUN5 loss generates an unmethylated status at the C3782 position of 28S rRNA that drives an overall depletion of protein synthesis, and leads to the emergence of an adaptive translational program for survival under conditions of cellular stress. Interestingly, NSUN5 epigenetic inactivation also renders these gliomas sensitive to bioactivatable substrates of the stress-related enzyme NQO1. Most importantly, NSUN5 epigenetic inactivation is a hallmark of glioma patients with long-term survival for this otherwise devastating disease.
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Majem B, Parrilla A, Jiménez C, Suárez-Cabrera L, Barber M, Marín A, Castellví J, Tamayo G, Moreno-Bueno G, Ponce J, Matias-Guiu X, Alameda F, Romero I, Sánchez JL, Pérez-Benavente A, Moran S, Esteller M, Reventós J, Rigau M, Gil-Moreno A, Segura MF, Santamaría A

MicroRNA-654-5p suppresses ovarian cancer development impacting on MYC, WNT and AKT pathways.

Oncogene Ago 2019, 38 (32) 6035-6050. Epub 5 Jul 2019
Ovarian cancer is the most lethal gynecological malignancy due to the silent nature on its early onset and the rapid acquisition of drug resistance. Histologically heterogeneous, it includes several subtypes with different mutational landscapes, hampering the development of effective targeted therapies. Non-coding RNAs are emerging as potential new therapeutic targets in cancer. To search for a microRNA signature related to ovarian carcinomas and study its potential as effective targeted therapy, we examined the expression of 768 miRNA in a large collection of tumor samples and found miR-654-5p to be infraexpressed in ovarian serous carcinomas, the most common and aggressive type. Restoration of miR-654-5p levels reduced tumor cell viability in vitro and in vivo and impaired sphere formation capacity and viability of ovarian cancer patient-derived ascitic cells ex vivo. CDCP1 and PLAGL2 oncogenes were found to be the most relevant direct miR-654-5p targets and both genes convey in a molecular signature associated with key cancer pathways relevant to ovarian tumorigenesis, such as MYC, WNT and AKT pathways. Together, we unveiled the tumor suppressor function of miR-654-5p, suggesting that its restoration or co-targeting of CDCP1 and PLAGL2 may be an effective therapeutic approach for ovarian cancer.
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Montal R, Andreu-Oller C, Bassaganyas L, Esteban-Fabró R, Moran S, Montironi C, Moeini A, Pinyol R, Peix J, Cabellos L, Villanueva A, Sia D, Mazzaferro V, Esteller M, Llovet JM

Molecular portrait of high alpha-fetoprotein in hepatocellular carcinoma: implications for biomarker-driven clinical trials.

Br. J. Cancer Ago 2019, 121 (4) 340-343. Epub 9 Jul 2019
The clinical utility of serum alpha-fetoprotein (AFP) in patients with hepatocellular carcinoma (HCC) is widely recognised. However, a clear understanding of the mechanisms of AFP overexpression and the molecular traits of patients with AFP-high tumours are not known. We assessed transcriptome data, whole-exome sequencing data and DNA methylome profiling of 520 HCC patients from two independent cohorts to identify distinct molecular traits of patients with AFP-high tumours (serum concentration > 400 ng/ml), which represents an accepted prognostic cut-off and a predictor of response to ramucirumab. Those AFP-high tumours (18% of resected cases) were characterised by significantly lower AFP promoter methylation (p < 0.001), significant enrichment of progenitor-cell features (CK19, EPCAM), higher incidence of BAP1 oncogene mutations (8.5% vs 1.6%) and lower mutational rates of CTNNB1 (14% vs 30%). Specifically, AFP-high tumours displayed significant activation of VEGF signalling (p < 0.001), which might provide the rationale for the reported benefit of ramucirumab in this subgroup of patients.
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Suárez-Lledó M, Marcos MÁ, Cuatrecasas M, Bombi JA, Fernández-Avilés F, Magnano L, Martínez-Cibrián N, Llobet N, Rosiñol L, Gutiérrez-García G, Jorge S, Martínez C, Rovira M

Quantitative PCR Is Faster, More Objective, and More Reliable Than Immunohistochemistry for the Diagnosis of Cytomegalovirus Gastrointestinal Disease in Allogeneic Stem Cell Transplantation.

Biol. Blood Marrow Transplant. 17 Jul 2019, . Epub 17 Jul 2019
Diagnosis of gastrointestinal (GI) cytomegalovirus (CMV) disease relies on the presence of GI symptoms and detection of CMV, mainly by immunohistochemistry (IHC), in GI biopsy specimens. Thus, in a symptomatic patient, a positive CMV-IHC result is accepted as a diagnosis of CMV disease. However, a positive CMV-PCR in GI tissue is considered "possible" CMV disease. Therefore, it would be very useful if, in practice, both techniques showed equal sensitivity and reliability. This is because PCR has many practical advantages over IHC for detecting CMV. The aim of this study was to compare quantitative PCR with IHC for the diagnosis of GI CMV disease. A total of 186 endoscopic GI biopsy specimens from 123 patients with GI symptoms after an allogeneic stem cell transplantation (allo-SCT; 2004-2017) were analyzed by IHC and PCR on 113 paraffin-embedded and 73 fresh samples. The results were then compared. Of the patients with macroscopic lesions in the mucosa and CMV-IHC-positive biopsy specimens (eg, "proven" CMV disease, n = 28), all but 1 were CMV-PCR positive. Of the patients without macroscopic lesions in the mucosa and CMV-IHC-positive biopsy specimens (eg, probable CMV disease, n = 4), only 1 was CMV-PCR positive. Eight patients had CMV-IHC-negative/CMV-PCR-positive gut biopsy specimens. These cases fall within the current definition of possible CMV disease. In 6 of these 8 cases (75%), the viral load in GI tissue was very high (>10,000 copies/µg). Taken together, the results from the proven and probable cases revealed that CMV-PCR shows the same sensitivity (100%), specificity (98%), and positive (93%) and negative predictive value (100%) as CMV-IHC. Detection of CMV in fresh GI mucosa by quantitative PCR is as useful as IHC for the diagnosis of GI CMV disease. The results show that quantitative PCR has the same sensitivity, specificity, and positive/negative predictive value as IHC.
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Palomeras S, Diaz-Lagares Á, Viñas G, Setien F, Ferreira HJ, Oliveras G, Crujeiras AB, Hernández A, Lum DH, Welm AL, Esteller M, Puig T

Epigenetic silencing of TGFBI confers resistance to trastuzumab in human breast cancer.

Breast Cancer Res. 5 Jul 2019, 21 (1) 79. Epub 5 Jul 2019
Acquired resistance to trastuzumab is a major clinical problem in the treatment of HER2-positive (HER2+) breast cancer patients. The selection of trastuzumab-resistant patients is a great challenge of precision oncology. The aim of this study was to identify novel epigenetic biomarkers associated to trastuzumab resistance in HER2+ BC patients.
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