Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Serum magnesium in healthy pregnant women in a teaching hospital in South-South Nigeria

Context: Magnesium plays a crucial role in metabolism especially with respect to carbohydrate, protein and energy syntheses. Its decline in pregnancy has been associated with conditions like preeclampsia and preterm delivery. We assess the prevalence of hypomagnesaemia in our locale and examine the associated maternal characteristics.Objectives: The primary objective was to determine the level of serum magnesium at which hypomagnesaemia could be diagnosed, while secondary objective was to define maternal characteristics associated with hypomagnesaemia.Study Design, Setting and Subjects: A pilot study was done to document the mean serum magnesium level for the population of female patients attending UBTH. The main study was a cross-sectional study of healthy antenatal women recruited between 24 and 26 weeks of pregnancy. Serum magnesium estimates were done with samples collected at recruitment. The magnesium levels determined were used to divide the subjects into two groups of hypomagnesaemic and normomagnesaemic patients. Their sociodemographic characteristics were used to generate a database for analysis.Results: Serum magnesium levels were higher in the non-pregnant subjects than the pregnant women in the pilot study. The prevalence of magnesium deficiency in the main study was 16.25%. Hypomagnesaemia was more likely in teenagers (P=0.00), women of higher parities (P=0.02) and lower social class (P=0.00). Conclusion: Hypomagnesaemia in pregnancy is common in teenagers, women of high parity and low social class. Magnesium supplementation or consumption of magnesium-rich food is recommended for these groups of women, while discouraging too early, frequent or many deliveries.Keywords: serum magnesium, pregnant women, south-south NigeriaTrop J Obstet Gynaecol, 30 (1), April 201

Science and engineering of electrospun nanofibers for advances in clean energy, water filtration, and regenerative medicine

10.1007/s10853-010-4509-1Journal of Materials Science45236283-6312JMTS