esteller davalos merkel villasante

Dos ocells d'un tret: una anàlisi bioinformàtica millorada pot estimar les variacions del nombre de còpies genètiques a partir de dades epigenètiques

Un equip liderat pel Dr. Manel Esteller, director de l'Institut de Recerca contra la Leucèmia Josep Carreras, ha millorat la identificació computacional d'amplificacions de gens medicables en tumors, a partir de dades epigenètiques. Mitjançant aquesta nova eina, els científics poden tenir informació fiable sobre les dades moleculars d'un tumor en particular, tant a nivell genètic com epigenètic, fins i tot quan la mostra és escassa.

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Vista Ministra Diana Morant

L'Institut de Recerca contra la Leucèmia Josep Carreras ha estat seleccionat per l’Institut Nacional del Càncer dels Estats Units per al projecte del Proteoma Càncer amb el suport del Ministeri de Ciència i Innovació

L'Institut Josep Carreras entra a formar part del projecte Proteoma del Càncer, una iniciativa internacional per a l'estudi dels tumors malignes que compta amb el suport del Ministeri de Ciència i Innovació. La seva Ministra, la Diana Morant, va visitar el dijous l'Institut Josep Carreras i va anunciar una ajuda d'un milió d'euros per a impulsar el projecte.

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Grup Briones - Sant Pau

Finalitza la Fase I del primer assaig clínic CAR-T30 d’Europa, de producció pròpia, per a limfoma de Hodgkin i no-Hodgkin T

El primer assaig amb un medicament d’immunoteràpia CAR-T produït a Sant Pau, pioner a Europa, per al tractament del limfoma de Hodgkin clàssic i limfoma no-Hodgkin T CD30 + en recidiva o refractari, ha finalitzat la seva Fase I amb èxit. El projecte està liderat pel Dr. Javier Briones, cap de la Unitat d’Hematologia Clínica del Servei d’Hematologia de l’Hospital de Sant Pau i cap del Grup de recerca d’Immunoteràpia Cel·lular i Teràpia Gènica de l’Institut de Recerca de l’Hospital de Sant Pau - IIB-Sant Pau i l’Institut de Recerca contra la Leucèmia Josep Carreras. 

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220426 NdP Marta Palomo

Una anàlisi de sang permet distingir la COVID-19 greu de la preeclàmpsia en dones embarassades

L’equip d’investigadors encapçalat per Marta Palomo, de l’Institut de Recerca contra la Leucèmia Josep Carreras, i Fàtima Crispi, de BCNatal-IDIBAPS, ha identificat marcadors que permeten diferenciar-les. Aquests resultats, emmarcats en un projecte finançat per La Marató de TV3, obren la porta a un diagnòstic més precís d’aquestes malalties i a una millor avaluació del risc.

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Últimes publicacions

Genescà, E, González-Gil, C

Latest Contributions of Genomics to T-Cell Acute Lymphoblastic Leukemia (T-ALL)

Cancers 2022 17 Mai 2022, (14) 2474. Epub 17 Mai 2022
As for many neoplasms, initial genetic data about T-cell acute lymphoblastic leukemia (T-ALL) came from the application of cytogenetics. This information helped identify some recurrent chromosomal alterations in T-ALL at the time of diagnosis, although it was difficult to determine their prognostic impact because of their low incidence in the specific T-ALL cohort analyzed. Genetic knowledge accumulated rapidly following the application of genomic techniques, drawing attention to the importance of using high-resolution genetic techniques to detect cryptic aberrations present in T-ALL, which are not usually detected by cytogenetics. We now have a clearer appreciation of the genetic landscape of the different T-ALL subtypes at diagnosis, explaining the particular oncogenetic processes taking place in each T-ALL, and we have begun to understand relapse-specific mechanisms. This review aims to summarize the latest advances in our knowledge of the genome in T-ALL. We highlight areas where the research in this subtype of ALL is progressing with the aim of identifying key questions that need to be answered in the medium-long term if this knowledge is to be applied in clinics.
Blecua P, Davalos V, de Villasante I, Merkel A, Musulen E, Coll-SanMartin L, Esteller M

Refinement of computational identification of somatic copy number alterations using DNA methylation microarrays illustrated in cancers of unknown primary.

Brief Bioinform 6 Mai 2022, . Epub 6 Mai 2022
High-throughput genomic technologies are increasingly used in personalized cancer medicine. However, computational tools to maximize the use of scarce tissues combining distinct molecular layers are needed. Here we present a refined strategy, based on the R-package 'conumee', to better predict somatic copy number alterations (SCNA) from deoxyribonucleic acid (DNA) methylation arrays. Our approach, termed hereafter as 'conumee-KCN', improves SCNA prediction by incorporating tumor purity and dynamic thresholding. We trained our algorithm using paired DNA methylation and SNP Array 6.0 data from The Cancer Genome Atlas samples and confirmed its performance in cancer cell lines. Most importantly, the application of our approach in cancers of unknown primary identified amplified potentially actionable targets that were experimentally validated by Fluorescence in situ hybridization and immunostaining, reaching 100% specificity and 93.3% sensitivity.
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Garcia-Prieto CA, Martínez-Jiménez F, Valencia A, Porta-Pardo E

Detection of oncogenic and clinically actionable mutations in cancer genomes critically depends on variant calling tools.

Bioinformatics 5 Mai 2022, . Epub 5 Mai 2022
The analysis of cancer genomes provides fundamental information about its aetiology, the processes driving cell transformation or potential treatments. While researchers and clinicians are often only interested in the identification of oncogenic mutations, actionable variants or mutational signatures, the first crucial step in the analysis of any tumor genome is the identification of somatic variants in cancer cells (i.e., those that have been acquired during their evolution). For that purpose, a wide range of computational tools have been developed in recent years to detect somatic mutations in sequencing data from tumor samples. While there have been some efforts to benchmark somatic variant calling tools and strategies, the extent to which variant calling decisions impact the results of downstream analyses of tumor genomes remains unknown.
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Arribas AJ, Napoli S, Cascione L, Sartori G, Barnabei L, Gaudio E, Tarantelli C, Mensah AA, Spriano F, Zucchetto A, Rossi FM, Rinaldi A, De Moura MC, Jovic S, Bordone-Pittau R, Di Veroli A, Stathis A, Cruciani G, Stussi G, Gattei V, Brown JR, Esteller M, Zucca E, Rossi D, Bertoni F

Resistance to PI3κδ inhibitors in marginal zone lymphoma can be reverted by targeting the IL-6/PDGFRA axis.

Haematologica 28 Abr 2022, . Epub 28 Abr 2022
PI3KPPinhibitors are active in patients with lymphoid neoplasms and a first series of them have been approved for the treatment of multiple types of B-cell lymphoid tumors, including marginal zone lymphoma (MZL). The identification of the mechanisms underlying either primary or secondary resistance is fundamental to optimize the use of novel drugs. Here, we present a model of secondary resistance to PI3Kffinhibitors obtained by prolonged exposure of a splenic MZL cell line to idelalisib. The VL51 cell line was kept under continuous exposure to idelalisib. The study included detailed characterization of the model, pharmacological screens, silencing experiments, validation experiments on multiple cell lines and on clinical specimens. VL51 developed resistance to idelalisib, copanlisib, duvelisib, and umbralisib. An integrative analysis of transcriptome and methylation underlined an enrichment of up-regulated transcripts and lowmethylated promoters in resistant cells, including IL-6/STAT3 and PDGFRA related genes and surface CD19 expression, alongside the repression of the let-7 family miRNAs, of miR-125, miR-130, miR-193 and miR-20. The use of the IL-6R blocking antibody tocilizumab, the STAT3 inhibitor stattic, the LIN28 inhibitor LIN1632, the PDGFR inhibitor masitinib and the anti-CD19 antibody drug conjugate loncastuximab tesirine were active compounds in the resistant cells as single agents and/or in combination with PI3K//inhibition. Findings were validated on additional in vitro lymphoma models and on clinical specimens. A novel model of resistance obtained from splenic MZL allowed the identification of therapeutic approaches able to improve the anti-tumor activity of PI3Kttinhibitors in B-cell lymphoid tumors.
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Cao X, Li W, Wang T, Ran D, Davalos V, Planas-Serra L, Pujol A, Esteller M, Wang X, Yu H

Accelerated biological aging in COVID-19 patients.

Nat Commun 19 Abr 2022, 13 (1) 2135. Epub 19 Abr 2022
Chronological age is a risk factor for SARS-CoV-2 infection and severe COVID-19. Previous findings indicate that epigenetic age could be altered in viral infection. However, the epigenetic aging in COVID-19 has not been well studied. In this study, DNA methylation of the blood samples from 232 healthy individuals and 413 COVID-19 patients is profiled using EPIC methylation array. Epigenetic ages of each individual are determined by applying epigenetic clocks and telomere length estimator to the methylation profile of the individual. Epigenetic age acceleration is calculated and compared between groups. We observe strong correlations between the epigenetic clocks and individual's chronological age (r > 0.8, p < 0.0001). We also find the increasing acceleration of epigenetic aging and telomere attrition in the sequential blood samples from healthy individuals and infected patients developing non-severe and severe COVID-19. In addition, the longitudinal DNA methylation profiling analysis find that the accumulation of epigenetic aging from COVID-19 syndrome could be partly reversed at late clinic phases in some patients. In conclusion, accelerated epigenetic aging is associated with the risk of SARS-CoV-2 infection and developing severe COVID-19. In addition, the accumulation of epigenetic aging from COVID-19 may contribute to the post-COVID-19 syndrome among survivors.
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