Percorrer por data de Publicação, começado por "2025-05-25"
A mostrar 1 - 2 de 2
Resultados por página
Opções de ordenação
- Targetable Genetic Alterations in High-Risk Neuroblastoma Patients Enrolled in the SIOPEN HR-NBL1 StudyPublication . Anseri, Elnaz Saberi; Bellini, Angela; Pötschger, Ulrike; Taschner-Mandl, Sabine; Planchon, Julien Masliah; Attignon, Valéry; Auger, Nathalie; Beiske, Klaus; Goodmann, Angharad; Jeison, Marta; Mazzocco, Katia; Morini, Martina; Capasso, Mario; Mühlethaler-Mottet, Annick; Noguera, Rosa; Font de Mora, Jaime; Martinsson, Tommy; Van Roy, Nadine; Vicha, Ales; Marques, Barbara; Chesler, Louis; George, Sally; Tweddle, Deborah; Ladenstein, Ruth; Schleiermacher, GudrunBackground: In high-risk neuroblastoma (HR-NB), new treatment strategies, including targeted treatments, are required to improve outcomes. Aim: To determine the frequency of genetic alterations (SNVs/Indels) in genes considered to be targetable and/or to play a role in oncogenesis in HR-NB. Methods: Diagnostic tumor samples from 709 patients treated in the SIOPEN HR-NBL1 trial (INRG stage M: 636 patients; localized: 70 patients; Ms: 3 patients; 269 MYCN amplified) were analyzed. Targeted Sequencing (TrueSeq Custom Amplicon) of 85 genes involved in oncogenesis and therapy response was performed on (n=484 samples), along with other targeted sequencing approaches (n=377 samples), whole-exome sequencing (n=32 samples), and whole-genome sequencing (n=8 samples) across ten European centers. Final results were reported on the panel of 85 genes. Variant calling and copy number alterations were analyzed using Mutect2 and FACETS. Matched germline data were available for 54 patients.
- Comprehensive Genetic Analysis Provides Novel Insights Into The MicroRNA Regulatory Landscape of Autism Spectrum DisorderPublication . Marques, Ana Rita; Martiniano, Hugo; Santos, João Xavier; Vilela, Joana; Asif, Muhammad; Sousa, Lisete; Oliveira, Guiomar; Vicente, Astrid MouraBackground: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a strong genetic component. Many risk genes are associated with ASD, however most of the genetic determinants are still unknown and a role for gene regulatory mechanisms is likely. MicroRNAs (miRNAs) regulate gene expression, playing key roles in neural development and function, and have been implicated in ASD onset and progression. Methods: To identify miRNA potentially associated with ASD, we conducted a comprehensive analysis of Single Nucleotide Variants (SNVs) and Copy Number Variants (CNVs) from ASD patients (N = 4300 and N = 3570, respectively) and control subjects (N = 67442 and N = 9649, respectively). We further performed functional enrichment analysis to understand the functional impact of these miRNAs variants. Results: Our results identified 28 miRNAs significantly enriched for putative disrupted SNVs and 31 miRNAs exclusively or more frequently targeted by CNVs in ASD cases, when compared to controls (α=0.05). These genes encode 70 mature miRNAs, including some novel and others previously implicated in ASD, that are predicted to target 2745 brain-expressed genes. Functional analysis indicates they are enriched in processes such as cellular signaling, gene regulation, protein metabolism, and chromatin structure, all of which are critical for ASD development. Interestingly, 44 of the identified miRNAs are predicted to regulate 71 genes strongly associated with increased ASD risk. Conclusion: This comprehensive gene-based analysis highlights miRNAs that regulate gene networks and cellular pathways essential for brain function and plasticity, which are often disrupted in ASD patients.