Substitution mutational signatures in whole-genome-sequenced cancers in the UK population.

Whole-genome sequencing (WGS) permits comprehensive cancer genome analyses, revealing mutational signatures, imprints of DNA damage and repair processes that have arisen in each patient's cancer. We performed mutational signature analyses on 12,222 WGS tumor-normal matched pairs, from patients recruited via the UK National Health Service. We contrasted our results to two independent cancer WGS datasets, the International Cancer Genome Consortium (ICGC) and Hartwig Foundation, involving 18,640 WGS cancers in total. Our analyses add 40 single and 18 double substitution signatures to the current mutational signature tally. Critically, we show for each organ, that cancers have a limited number of 'common' signatures and a long tail of 'rare' signatures. We provide a practical solution for utilizing this concept of common versus rare signatures in future analyses.

Multi-tissue transcriptome analysis of two Begonia species reveals dynamic patterns of evolution in the chalcone synthase gene family.

Begonia is an important horticultural plant group, as well as one of the most speciose Angiosperm genera, with over 2000 described species. Genus wide studies of genome size have shown that Begonia has a highly variable genome size, and analysis of paralog pairs has previously suggested that Begonia underwent a whole genome duplication. We address the contribution of gene duplication to the generation of diversity in Begonia using a multi-tissue RNA-seq approach. We chose to focus on chalcone synthase (CHS), a gene family having been shown to be involved in biotic and abiotic stress responses in other plant species, in particular its importance in maximising the use of variable light levels in tropical plants. We used RNA-seq to sample six tissues across two closely related but ecologically and morphologically divergent species, Begonia conchifolia and B. plebeja, yielding 17,012 and 19,969 annotated unigenes respectively. We identified the chalcone synthase gene family members in our Begonia study species, as well as in Hillebrandia sandwicensis, the monotypic sister genus to Begonia, Cucumis sativus, Arabidopsis thaliana, and Zea mays. Phylogenetic analysis suggested the CHS gene family has high duplicate turnover, all members of CHS identified in Begonia arising recently, after the divergence of Begonia and Cucumis. Expression profiles were similar within orthologous pairs, but we saw high inter-ortholog expression variation. Sequence analysis showed relaxed selective constraints on some ortholog pairs, with substitutions at conserved sites. Evidence of pseudogenisation and species specific duplication indicate that lineage specific differences are already beginning to accumulate since the divergence of our study species. We conclude that there is evidence for a role of gene duplication in generating diversity through sequence and expression divergence in Begonia.

Prognostic Impact of let-7e MicroRNA and Its Target Genes in Localized High-Risk Intestinal GIST: A Spanish Group for Research on Sarcoma (GEIS) Study.

MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level, and they have been described as being associated with tumor prognosis. Here, miRNA profiling was planned to explore new molecular prognostic biomarkers in localized intestinal high-risk GIST. Paraffin tumor blocks of 14 and 86 patients were used in the discovery and expansion sets, respectively. GeneChip miRNA v3.0 was employed to identify the miRNAs differentially expressed between relapsed and non-relapsed patient samples, which were validated in the expansion set, by qRT-PCR. RT2 Profiler PCR Array was used for the screening of let-7e targets. Expression levels were correlated with relapse-free survival and overall survival. In the discovery set, 39 miRNAs were significantly deregulated, let-7e and miR-550 being the most underexpressed and overexpressed miRNAs in the relapsed group, respectively. In the expansion set, the underexpression of let-7e or the overexpression of 4 of its target genes (ACVR1B, CASP3, COL3A1, and COL5A2) were statistically associated with worse relapse-free survival. The expression of let-7e and 4 of its target genes are potential prognostic biomarkers in high-risk localized intestinal GIST. The expression of these genes is a potential molecular tool useful for a more accurate prognosis in this subset of GIST patients.

Acompañamiento familiar en la hospitalización del usuario pediátrico de 6 a 12 años / Family support during hospitalization of the 6 to 12 years old pediatric user

Antecedentes. La hospitalización genera en el niño una adaptación al nuevo entorno, situación que produce estrés producto del cambio de ambiente, en donde la separación de sus padres de su entorno típico es un tema interesante de abordar para comprender el perfil del acompañante. Objetivo. Describir los tipos de acompañamiento familiar más frecuentes durante la hospitalización del usuario pediátrico de 6 a 12 años en el Centro de Costo Indiferenciado del Niño y la Niña (CCINN), del Complejo Asistencial Dr. Víctor Ríos Ruiz de la ciudad de Los Ángeles, Chile. Material y método. Estudio descriptivo de corte transversal, en el cual se seleccionó a 52 usuarios pediátricos entre 6 a 12 años hospitalizados en el CCINN del Complejo Asistencial Dr. Víctor Ríos Ruiz de Los Ángeles. Resultados. El 92,3 por ciento de los padres y/o cuidadores que visitan a sus hijos están interesados en entender la situación actual del niño/a en su hospitalización y enfermedad (acompañamiento familiar tipo 1), mientras que un 7,7 por ciento de la muestra de padres con un esfuerzo disminuido (acompañamiento familiar tipo 2) (z=4,10; p<0,001), no registrando padres y/o cuidadores con conductas de bajo o escaso interés por la situación actual del niño/a que pudiera dificultar su integración frente a la situación de hospitalización y enfermedad (acompañamiento familiar tipo 3). Conclusión. Se logra evidenciar una preocupación de los padres y/o cuidadores por el proceso que vive el hijo y/o pupilo, en donde los profesionales pueden integrarse mediante la educación de técnicas o materias del cuidado posthospitalización del usuario pediátrico.

Background. The hospital generates in the child adaptation to a new environment, a situation that produces stress because of the change, where the separation of their parents from their typical environment is an interesting topic to address in order to understand the profile of the accompanying person. Objective. To describe the types of most frequent family company observed during the hospitalization of the 6 to 12 years old pediatric user in the Child Undifferentiated Cost Center (UCCCh). Methods. Cross-sectional descriptive study, which selected 52 pediatric users aged 6 to 12, hospitalized in UCCCh at Dr. Víctor Ríos Ruiz Hospital, Los Ángeles, Chile. Results. 92.3 percent of parents and / or caregivers who visit their children are interested in understand the current situation of the child in his/her hospitalization and illness (family support type 1), while 7.7 percent of the sample shows declined efforts of parents (family support type 2) (z=4.10, P<0.001), not registering parents / caregivers with a behavior that shows low or poor interest in the child’s current situation / that could impede their integration addressing the situation of hospitalization and illness (family support type 3). Conclusion. It does demonstrate a concern from parents/caregivers through the process experienced by the child, where professionals can integrate them through education techniques or some care contents post-hospitalization for pediatric user.