Recomendaciones para la implementación del Artículo 37 Difusión en Acceso Abierto de la Ley de la Ciencia, la Tecnología y la Innovación

Guía práctica que define los aspectos principales de la política nacional de acceso abierto y especifica cuáles son los nuevos roles que habrán de adoptar los colectivos implicados en la producción y gestión del mercado de la información científica. Contiene un capítulo de recomendaciones específicas para gestores de ayudas públicas a la I+D+i, otro para las universidades y centros de investigación, otro para los investigadores y otro para las entidades suscriptoras de revistas científicas. Este documento ha sido coordinado por FECYT en el marco de las actividades de RECOLECTA, cuyas actuaciones se enmarcan en el convenio de colaboración con REBIUN

Identification of gene mutations and fusion genes in patients with Sézary Syndrome

Sézary syndrome is a leukemic form of cutaneous T-cell lymphoma with an aggressive clinical course. The genetic etiology of the disease is poorly understood, with chromosomal abnormalities and mutations in some genes being involved in the disease. The goal of our study was to understand the genetic basis of the disease by looking for driver gene mutations and fusion genes in 15 erythrodermic patients with circulating Sézary cells, 14 of them fulfilling the diagnostic criteria of Sézary syndrome. We have discovered genes that could be involved in the pathogenesis of Sézary syndrome. Some of the genes that are affected by somatic point mutations include ITPR1, ITPR2, DSC1, RIPK2, IL6, and RAG2, with some of them mutated in more than one patient. We observed several somatic copy number variations shared between patients, including deletions and duplications of large segments of chromosome 17. Genes with potential function in the T-cell receptor signaling pathway and tumorigenesis were disrupted in Sézary syndrome patients, for example, CBLB, RASA2, BCL7C, RAMP3, TBRG4, and DAD1. Furthermore, we discovered several fusion events of interest involving RASA2, NFKB2, BCR, FASN, ZEB1, TYK2, and SGMS1. Our work has implications for the development of potential therapeutic approaches for this aggressive disease

Optical genome mapping: a promising new tool to assess genomic complexity in chronic lymphocytic leukemia (CLL)

Novel treatments in chronic lymphocytic leukemia (CLL) have generated interest regarding the clinical impact of genomic complexity, currently assessed by chromosome banding analysis (CBA) and chromosomal microarray analysis (CMA). Optical genome mapping (OGM), a novel technique based on imaging of long DNA molecules labeled at specific sites, allows the identification of multiple cytogenetic abnormalities in a single test. We aimed to determine whether OGM is a suitable alternative to cytogenomic assessment in CLL, especially focused on genomic complexity. Cytogenomic OGM aberrations from 42 patients were compared with CBA, FISH, and CMA information. Clinical-biological characteristics and time to first treatment (TTFT) were analyzed according to the complexity detected by OGM. Globally, OGM identified 90.3% of the known alterations (279/309). Discordances were mainly found in (peri-)centromeric or telomeric regions or subclonal aberrations (<15-20%). OGM underscored additional abnormalities, providing novel structural information on known aberrations in 55% of patients. Regarding genomic complexity, the number of OGM abnormalities had better accuracy in predicting TTFT than current methods (C-index: 0.696, 0.602, 0.661 by OGM, CBA, and CMA, respectively). A cut-off of ≥10 alterations defined a complex OGM group (C-OGM, n = 12), which included 11/14 patients with ≥5 abnormalities by CBA/CMA and one patient with chromothripsis (Kappa index = 0.778; p < 0.001). Moreover, C-OGM displayed enrichment of TP53 abnormalities (58.3% vs. 3.3%, p < 0.001) and a significantly shorter TTFT (median: 2 vs. 43 months, p = 0.014). OGM is a robust technology for implementation in the routine management of CLL patients, although further studies are required to define standard genomic complexity criteria

Optical Genome Mapping: A Promising New Tool to Assess Genomic Complexity in Chronic Lymphocytic Leukemia (CLL)

Novel treatments in chronic lymphocytic leukemia (CLL) have generated interest regarding the clinical impact of genomic complexity, currently assessed by chromosome banding analysis (CBA) and chromosomal microarray analysis (CMA). Optical genome mapping (OGM), a novel technique based on imaging of long DNA molecules labeled at specific sites, allows the identification of multiple cytogenetic abnormalities in a single test. We aimed to determine whether OGM is a suitable alternative to cytogenomic assessment in CLL, especially focused on genomic complexity. Cytogenomic OGM aberrations from 42 patients were compared with CBA, FISH, and CMA information. Clinical–biological characteristics and time to first treatment (TTFT) were analyzed according to the complexity detected by OGM. Globally, OGM identified 90.3% of the known alterations (279/309). Discordances were mainly found in (peri-)centromeric or telomeric regions or subclonal aberrations (n = 12), which included 11/14 patients with ≥5 abnormalities by CBA/CMA and one patient with chromothripsis (Kappa index = 0.778; p TP53 abnormalities (58.3% vs. 3.3%, p p = 0.014). OGM is a robust technology for implementation in the routine management of CLL patients, although further studies are required to define standard genomic complexity criteria

Identification of gene mutations and fusion genes in patients with Sézary syndrome.

Sézary syndrome is a leukemic form of cutaneous T-cell lymphoma with an aggressive clinical course. The genetic etiology of the disease is poorly understood, with chromosomal abnormalities and mutations in some genes being involved in the disease. The goal of our study was to understand the genetic basis of the disease by looking for driver gene mutations and fusion genes in 15 erythrodermic patients with circulating Sézary cells, 14 of them fulfilling the diagnostic criteria of Sézary syndrome. We have discovered genes that could be involved in the pathogenesis of Sézary syndrome. Some of the genes that are affected by somatic point mutations include ITPR1, ITPR2, DSC1, RIPK2, IL6, and RAG2, with some of them mutated in more than one patient. We observed several somatic copy number variations shared between patients, including deletions and duplications of large segments of chromosome 17. Genes with potential function in the T-cell receptor signaling pathway and tumorigenesis were disrupted in Sézary syndrome patients, for example, CBLB, RASA2, BCL7C, RAMP3, TBRG4, and DAD1. Furthermore, we discovered several fusion events of interest involving RASA2, NFKB2, BCR, FASN, ZEB1, TYK2, and SGMS1. Our work has implications for the development of potential therapeutic approaches for this aggressive disease.This project was funded by “Retos de la Sociedad 2013: Europa Redes y Gestores” Programme from the Spanish Ministry of Economy and Competitiveness no. SAF2013-49108-R (to XE) and RD12/0036/0044 Red Temática de Investigación Cooperativa en Cancer, Fondo Europeo de Desarrollo Regional (to BE, FG, and RP), the Generalitat de Catalunya AGAUR 2014 SGR-1138 (to XE) and 2014 SGR-585 (to BE, A Puiggros, and FG), the European Commission 7th Framework Program (FP7/2007-2013) under grant agreement 282510 (A BLUEPRINT of haematopoietic Epigenomes to XE) and 262055 (European Sequencing and Genotyping Infrastructure to XE), Instituto de Salud Carlos III FEDER (PT13/0010/0005), and the “Xarxa de Bancs de tumors sponsored by Pla Director d’Oncologia de Catalunya.” We would also like to thank “Xarxa de Limfomes Cutanis de Catalunaya.” A Prasad is a Marie Curie Postdoctoral fellow supported by the European Commission 7th framework program (FP7/2007-2013) under grant agreement no. 625356. We acknowledge the support of the Spanish Ministry of Economy and Competitiveness, Centro de Excelencia Severo Ochoa 2013-2017, SEV-2012-0208

Recomendaciones para la implementación del artículo 37 Difusión en Acceso Abierto de la Ley de la Ciencia, la Tecnología y la Innovación

La Ley de la Ciencia, la Tecnología y la Innovación, publicada en junio de 20111, recoge en su artículo 37 los principales aspectos a tener en cuenta a la hora de llevar a cabo la difusión en abierto de los resultados de la investigación financiada con fondos públicos y aceptados para su publicación en publicaciones de investigación seriadas o periódicas. Sin embargo, las dudas que han surgido en los diferentes ámbitos de aplicación han motivado la realización de un ejercicio de reflexión que permita ordenar cuáles son los pasos que los diferentes agentes involucrados deberían abordar para un correcto cumplimiento de la normativa legal y facilitar así la adecuada aplicación del artículo sobre “Difusión en acceso abierto”. El objetivo de este documento es contar con una guía práctica que defina los aspectos principales de la política nacional de acceso abierto y despeje el camino a todos los actores afectados, al especificar cuáles son los nuevos roles que habrán de adoptarse y elaborar una serie de recomendaciones destinadas a todos los colectivos implicados en la producción y gestión del mercado de la información científica..

Optical genome mapping:a promising new tool to assess genomic complexity in chronic lymphocytic leukemia (CLL)

Abstract Novel treatments in chronic lymphocytic leukemia (CLL) have generated interest regarding the clinical impact of genomic complexity, currently assessed by chromosome banding analysis (CBA) and chromosomal microarray analysis (CMA). Optical genome mapping (OGM), a novel technique based on imaging of long DNA molecules labeled at specific sites, allows the identification of multiple cytogenetic abnormalities in a single test. We aimed to determine whether OGM is a suitable alternative to cytogenomic assessment in CLL, especially focused on genomic complexity. Cytogenomic OGM aberrations from 42 patients were compared with CBA, FISH, and CMA information. Clinical–biological characteristics and time to first treatment (TTFT) were analyzed according to the complexity detected by OGM. Globally, OGM identified 90.3% of the known alterations (279/309). Discordances were mainly found in (peri-)centromeric or telomeric regions or subclonal aberrations (<15–20%). OGM underscored additional abnormalities, providing novel structural information on known aberrations in 55% of patients. Regarding genomic complexity, the number of OGM abnormalities had better accuracy in predicting TTFT than current methods (C-index: 0.696, 0.602, 0.661 by OGM, CBA, and CMA, respectively). A cut-off of ≥10 alterations defined a complex OGM group (C-OGM, n = 12), which included 11/14 patients with ≥5 abnormalities by CBA/CMA and one patient with chromothripsis (Kappa index = 0.778; p < 0.001). Moreover, C-OGM displayed enrichment of TP53 abnormalities (58.3% vs. 3.3%, p < 0.001) and a significantly shorter TTFT (median: 2 vs. 43 months, p = 0.014). OGM is a robust technology for implementation in the routine management of CLL patients, although further studies are required to define standard genomic complexity criteria

Ús i abús de la natura, impactes i propostes de gestió. El cas de Catalunya com a paradigma

78 pages, 10 figures, 20 tablesFem aquí un balanç dels darrers quaranta anys d'ús, en molts casos abús, dels recursos naturals a Catalunya, un país representatiu dels països europeus, en especial dels mediterranis. [...]Peer reviewe