Multigene germline testing usefulness instead of BRCA1/2 single screening in triple negative breast cancer cases

Producción CientíficaTriple negative breast cancer is considered as the worst aggressive subtype with poor prognosis. Recent studies suggest a hereditary component is involve in TNBC development, especially in young patients. However, genetic spectrum remains unclear. Our purpose was to evaluate the usefulness of multigene panel testing in triple negative patients respect overall breast cancer cases as well as contributing to elucidate which genes are most implicated in TNBC development with respect to the remaining breast cancer subtypes. A breast cancer patients sample comprised of 100 triple negative breast cancer patients and 100 other breast cancer subtypes patients were analyzed by Next-Generation Sequencing using an On-Demand panel which included 35 predisposition cancer genes associated with inherited cancer susceptibility. Triple negative breast cancer patients obtained a higher percentage of germline variant carriers. ATM, PALB2, BRIP1 and TP53 were the most non-BRCA mutated genes. Moreover, triple negative breast cancer patients without family history related which proved to be carriers were diagnosed at significant earlier age. As conclusion, our study reinforces the usefulness of multigene panel testing in breast cancer cases but specifically in those with triple negative subtype regardless family history.Junta de Castilla y León. Dirección Regional de Salud de Castilla y León (GRS/2180/A/2020 y GRS/2351/A/2021

Informe nº 05

Muestras de especies de interés pesquero, procedentes de la plataforma continental y las costas de Galicia, recogidas en diciembre de 2002 (Campaña “Prestige-Plataforma 1202”) y enero de 2003 (Campaña “Prestige-Plataforma 0103”), han sido analizadas en el Centro Oceanográfico de Vigo del IEO para determinar su contenido en hidrocarburos aromáticos policíclicos (PAHs). Las especies analizadas han sido: rapes (Lophius spp.), gallo (Lepidorhombus boscii), merluza (Merluccius merluccius), lirio (Micromesistius poutassou), percebe (Polycipes cornucopia), navaja (Ensis ensis) y erizo (Paracentrotus lividus). La metodología empleada se basa en Cromatografía líquida de alta eficacia, con detector de fluorescencia con longitud de onda programable

Integrative analysis of DNA copy number, DNA methylation and gene expression in multiple myeloma reveals alterations related to relapse

Multiple myeloma (MM) remains incurable despite the introduction of novel agents, and a relapsing course is observed in most patients. Although the development of genomic technologies has greatly improved our understanding of MM pathogenesis, the mechanisms underlying relapse have been less thoroughly investigated. In this study, an integrative analysis of DNA copy number, DNA methylation and gene expression was conducted in matched diagnosis and relapse samples from MM patients. Overall, the acquisition of abnormalities at relapse was much more frequent than the loss of lesions present at diagnosis, and DNA losses were significantly more frequent in relapse than in diagnosis samples. Interestingly, copy number abnormalities involving more than 100 Mb of DNA at relapse significantly affect the gene expression of these samples, provoking a particular deregulation of the IL-8 pathway. On the other hand, no significant modifications of gene expression were observed in those samples with less than 100 Mb affected by chromosomal changes. Although several statistical approaches were used to identify genes whose abnormal expression at relapse was regulated by methylation, only two genes that were significantly deregulated in relapse samples (SORL1 and GLT1D1) showed a negative correlation between methylation and expression. Further analysis revealed that DNA methylation was involved in regulating SORL1 expression in MM. Finally, relevant changes in gene expression observed in relapse samples, such us downregulation of CD27 and P2RY8, were most likely not preceded by alterations in the corresponding DNA. Taken together, these results suggest that the genomic heterogeneity described at diagnosis remains at relapse.This work was partially supported by the Instituto de Salud Carlos III-Cofinanciación con fondos FEDER (PI080568, PS0901897 and PI13/00111), the Gerencia Regional de Salud, Junta de Castilla y León (GRS202/A08 and GRS 702/A/11), the Spanish Myeloma Network Program (RD06/0020/0006) and the Asociación Española Contra el Cáncer (AECC, GCB120981SAN).Peer Reviewe

Informe nº 0

Este informe presenta información sobre las concentraciones de hidrocarburos poliaromáticos totales presentes en el sedimento en muestras correspondientes a 23 estaciones localizadas en la plataforma continental gallega, recogidas en la Campaña oceanográfica 'PRESTIGE - CONTAMINACIÓN 1202', realizada a bordo del B/O Cornide de Saavedra del 7 al 13 de diciembre de 2002

Informe nº 13a

En el Centro Oceanográfico de Vigo del IEO han sido analizadas muestras de especies de peces pelágicos, recogidas durante la campaña Prestige-Pelágicos 0303 en la costa del Cantábrico. Las especies estudiadas han sido: caballa (Scomber scombrus), sardina (Sardina pilchardus) y jurel (Trachurus trachurus)

Transcriptome analysis reveals molecular profiles associated with evolving steps of monoclonal gammopathies

This is an open-access paper.-- et al.A multistep model has been proposed of disease progression starting in monoclonal gammopathy of undetermined significance continuing through multiple myeloma, sometimes with an intermediate entity called smoldering myeloma, and ending in extramedullary disease. To gain further insights into the role of the transcriptome deregulation in the transition from a normal plasma cell to a clonal plasma cell, and from an indolent clonal plasma cell to a malignant plasma cell, we performed gene expression profiling in 20 patients with monoclonal gammopathy of undetermined significance, 33 with high-risk smoldering myeloma and 41 with multiple myeloma. The analysis showed that 126 genes were differentially expressed in monoclonal gammopathy of undetermined significance, smoldering myeloma and multiple myeloma as compared to normal plasma cell. Interestingly, 17 and 9 out of the 126 significant differentially expressed genes were small nucleolar RNA molecules and zinc finger proteins. Several proapoptotic genes (AKT1 and AKT2) were down-regulated and antiapoptotic genes (APAF1 and BCL2L1) were up-regulated in multiple myeloma, both symptomatic and asymptomatic, compared to monoclonal gammopathy of undetermined significance. When we looked for those genes progressively modulated through the evolving stages of monoclonal gammopathies, eight snoRNA showed a progressive increase while APAF1, VCAN and MEGF9 exhibited a progressive downregulation. In conclusion, our data show that although monoclonal gammopathy of undetermined significance, smoldering myeloma and multiple myeloma are not clearly distinguishable groups according to their gene expression profiling, several signaling pathways and genes were significantly deregulated at different steps of the transformation process.This study was partially supported by Spanish FIS (PI080568, PS09/01450 and PS0901897), “Gerencia Regional de Salud, Junta de Castilla y León” (GRS 702/A/11) grant, and the Spanish Myeloma Network Program (RD06/0020/0006, RD12/0036/0058 and RD12/0036/0046).Peer Reviewe

Síndrome urémico hemolítico: eco-epidemiología del enemigo que afecta la seguridad alimentaria

Escherichia coli verocitotoxigénico (VTEC) es un patógeno emergente asociado a casos de diarrea, colitis hemorrágica y síndrome urémico hemolítico (SUH), del cual Argentina presenta el registro más alto de casos a nivel mundial. No existe tratamiento específico para el SUH, por lo que son fundamentales las estrategias de control y prevención. Los estudios se han centralizado en cepas del serotipo O157:H7, pero las infecciones asociadas a VTEC no-O157 tienen creciente importancia y representan nuevos desafíos para el diagnóstico y el control de VTEC. En este trabajo se evaluó el rol de distintas especies animales, medio ambiente y alimentos en la epidemiología de VTEC, se caracterizó la variabilidad genética y la virulencia de las cepas, y se estudiaron medidas de control. Las metodologías comprenden técnicas microbiológicas y de biología molecular. Los resultados confirman la amplia distribución de las cepas VTEC, demuestran su gran diversidad genética y la presencia de factores de virulencia asociados con enfermedad en el hombre. Las cepas estudiadas mostraron alta capacidad para sobrevivir en el ambiente. La exhaustiva caracterización de las cepas resalta el alto riesgo para la salud pública que representan.Trabajo presentado por el Centro de Investigación Veterinaria de Tandil (CIVETAN)

The RecD2 helicase balances RecA activities

DNA helicases of the RecD2 family are ubiquitous. Bacillus subtilis RecD2 in association with the single-stranded binding protein SsbA may contribute to replication fork progression, but its detailed action remains unknown. In this work, we explore the role of RecD2 during DNA replication and its interaction with the RecA recombinase. RecD2 inhibits replication restart, but this effect is not observed in the absence of SsbA. RecD2 slightly affects replication elongation. RecA inhibits leading and lagging strand synthesis, and RecD2, which physically interacts with RecA, counteracts this negative effect. In vivo results show that recD2 inactivation promotes RecA–ssDNA accumulation at low mitomycin C levels, and that RecA threads persist for a longer time after induction of DNA damage. In vitro, RecD2 modulates RecA-mediated DNA strand-exchange and catalyzes branch migration. These findings contribute to our understanding of how RecD2 may contribute to overcome a replicative stress, removing RecA from the ssDNA and, thus, it may act as a negative modulator of RecA filament growth