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

Changes in the chemistry of shallow groundwater related to the 2008 injection of CO2 at the ZERT field site, Bozeman, Montana

Approximately 300 kg/day of food-grade CO2 was injected through a perforated pipe placed horizontally 2–2.3 m deep during July 9–August 7, 2008 at the MSU-ZERT field test to evaluate atmospheric and near-surface monitoring and detection techniques applicable to the subsurface storage and potential leakage of CO2. As part of this multidisciplinary research project, 80 samples of water were collected from 10 shallow monitoring wells (1.5 or 3.0 m deep) installed 1–6 m from the injection pipe, at the southwestern end of the slotted section (zone VI), and from two distant monitoring wells. The samples were collected before, during, and following CO2 injection. The main objective of study was to investigate changes in the concentrations of major, minor, and trace inorganic and organic compounds during and following CO2 injection. The ultimate goals were (1) to better understand the potential of groundwater quality impacts related to CO2 leakage from deep storage operations, (2) to develop geochemical tools that could provide early detection of CO2 intrusion into underground sources of drinking water (USDW), and (3) to test the predictive capabilities of geochemical codes against field data. Field determinations showed rapid and systematic changes in pH (7.0–5.6), alkalinity (400–1,330 mg/l as HCO3), and electrical conductance (600–1,800 μS/cm) following CO2 injection in samples collected from the 1.5 m-deep wells. Laboratory results show major increases in the concentrations of Ca (90–240 mg/l), Mg (25–70 mg/l), Fe (5–1,200 ppb), and Mn (5–1,400 ppb) following CO2 injection. These chemical changes could provide early detection of CO2 leakage into shallow groundwater from deep storage operations. Dissolution of observed carbonate minerals and desorption-ion exchange resulting from lowered pH values following CO2 injection are the likely geochemical processes responsible for the observed increases in the concentrations of solutes; concentrations generally decreased temporarily following four significant precipitation events. The DOC values obtained are 5 ± 2 mg/l, and the variations do not correlate with CO2 injection. CO2 injection, however, is responsible for detection of BTEX (e.g. benzene, 0–0.8 ppb), mobilization of metals, the lowered pH values, and increases in the concentrations of other solutes in groundwater. The trace metal and BTEX concentrations are all significantly below the maximum contaminant levels (MCLs). Sequential leaching of core samples is being carried out to investigate the source of metals and other solutes

Quality Changes of Dehydrated Restructured Fish Product from Silver Carp (Hypophthalmichthys molitrix) as Affected by Drying Methods

10.1007/s11947-012-0812-yFood and Bioprocess Technology671664-168

The role of the financial sector in economic development: the Malaysian case

Financial development, Economic development, Malaysia, VECM, O16, G18, G28,