Methylome sequencing for fibrolamellar hepatocellular carcinoma depicts distinctive features

<p>With the goal of studying epigenetic alterations in fibrolamellar hepatocellular carcinoma (FLC) and establish an associated DNA methylation signature, we analyzed <i>LINE-1</i> methylation in a cohort of FLC and performed next-generation sequencing of DNA methylation in a training set of pure-FLCs and non-cirrhotic hepatocellular carcinomas (nc-HCC). DNA methylation was correlated with gene expression. Furthermore, we established and validated an epigenetic signature differentiating pure-FLC from other HCCs. <i>LINE-1</i> methylation correlated with shorter recurrence-free survival and overall survival in resected pure-FLC patients. Unsupervised clustering using CG sites located in islands distinguished pure-FLC from nc-HCC. Major DNA methylation changes occurred outside promoters, mainly in gene bodies and intergenic regions located in the vicinity of liver developmental genes (i.e., <i>SMARCA4</i> and <i>RXRA</i>). Partially methylated domains were more prone to DNA methylation changes. Furthermore, we identified several putative tumor suppressor genes (e.g., <i>DLEU7</i>) and oncogenes (e.g., <i>DUSP4</i>). While ∼70% of identified gene promoters gaining methylation were marked by bivalent histone marks (H3K4me3/H3K27me3) in embryonic stem cells, ∼70% of those losing methylation were marked by H3K4me3. Finally, we established a pure FLC DNA methylation signature and validated it in an independent dataset. Our analysis reveals a distinct epigenetic signature of pure FLC as compared to nc-HCC, with DNA methylation changes occurring in the vicinity of liver developmental genes. These data suggest new options for targeting FLC based on cancer epigenome aberrations.</p

Pixel-Bit

Resumen tomado de la publicaciónSe presenta una investigación sobre la utilización de dispositivos móviles de apoyo a la interpretación instrumental del alumnado de música de Educación Secundaria. El principal objetivo de esta investigación radica en analizar la eficacia de la utilización del teléfono móvil con microcontenidos para mejorar el rendimiento interpretativo de los alumnos.A través de la grabación en vídeo de los alumnos participantes y del diseño de partituras de control se ha logrado hacer un seguimiento minucioso de la interpretación instrumental, lo que ha permitido contar con datos valiosos del impacto del uso de las tecnologías móviles en este ámbito musical.Las conclusiones de este artículo demuestran que los alumnos que utilizan dispositivos móviles con microcontenidos cometen menos errores en la concatenación de dichos micro-contenidos que aquellos que no los utilizan, consiguiendo una mayor musicalidad. Igualmente, se pone en evidencia que dichos alumnos cometen menos errores puntuales de nota, lo que demuestra un mayor domino con el instrumento.ES

Additional file 5: of Prognostic impact of blood and urinary angiogenic factor levels at diagnosis and during treatment in patients with osteosarcoma: a prospective study

Table S3. Association between serum VEGF and bFGF and urinary bFGF levels at diagnosis and the risk of a poor histological response or treatment failure (multivariable analysis) (DOCX 16 kb