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

Size evolution and surface characterization of solid-state nanopores in different aqueous solutions

The stability and surface evolution of solid-state nanopores in aqueous solutions are extremely important since they would get immersed in solutions during DNA translocation experiment for DNA analyses. In this work, we systematically studied the size evolution of SiN nanopores in ethanol, deionized water and potassium chloride (KCl) solutions by careful surface characterization and composition analyses using a transmission electron microscope. Surprisingly, we found that nanopores closed up completely in ethanol in an hour and showed a 30% and 20% size decrease in deionized water and KCl solutions, respectively. Strong evidence of surface oxidation was found by composition analyses in the nanopore area. Nanopore size evolution was strongly dependent on initial pore size and solution pH value. In pH 13 KCl solution, SiN nanopores were observed to increase in size instead of decrease. The results not only provide useful information for DNA detection based on solid-state nanopores, but can also guide design and application of other nanodevices exposed to electrolyte-solvent systems such as cell-on-a-chip devices and biosensors.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000300433700027&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Chemistry, MultidisciplinaryNanoscience & NanotechnologyMaterials Science, MultidisciplinaryPhysics, AppliedSCI(E)PubMed4ARTICLE51572-1576