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

Shape, transverse size, and charged-hadron multiplicity of jets in pp collisions at sqrts=7;TeV sqrt {s} = 7;TeV

Measurements of jet characteristics from inclusive jet production in proton-proton collisions at a centre-of-mass energy of 7 TeV are presented. The data sample was collected with the CMS detector at the LHC during 2010 and corresponds to an integrated luminosity of 36 inverse picobarns. The mean charged hadron multiplicity, the differential and integral jet shape distributions, and two independent moments of the shape distributions are measured as functions of the jet transverse momentum for jets reconstructed with the anti-kT algorithm. The measured observables are corrected to the particle level and compared with predictions from various QCD Monte Carlo generators.Comment: Replaced with published version. Added journal reference and DOI. Supplementary data tables availabl

Search for a light charged Higgs boson in top quark decays in pp collisions at sqrt(s) = 7 TeV

Submitted to the Journal of High Energy Physics; see paper for full list of authorsResults are presented on a search for a light charged Higgs boson that can be produced in the decay of the top quark to charged H and b quark and which, in turn, decays into tau and tau neutrino. The analysed data correspond to an integrated luminosity of about 2 inverse femtobarns recorded in proton-proton collisions at sqrt(s) = 7 TeV by the CMS experiment at the LHC. The search is sensitive to the decays of the top quark pairs t anti-t to charged Higgs W b anti-b and t anti-t to charged Higgs b anti-b. Various final states have been studied separately, all requiring presence of a tau lepton from charged Higgs decays, missing transverse energy, and multiple jets. Upper limits on the branching fraction B(t to charged Higgs b) in the range of 2-3% are established for charged Higgs boson masses between 80 and 160 GeV, under the assumption that B(charged Higgs to tau anti-tau neutrino) = 1